Revisiting ovarian cancer microenvironment: a friend or a foe?
Boyi Zhang, Fei Chen, Qixia Xu, Liu Han, Jiaqian Xu, Libin Gao, Xiaochen Sun, Yiwen Li, Yan Li, Min Qian, Yu Sun
Revisiting ovarian cancer microenvironment: a friend or a foe?
Development of ovarian cancer involves the co-evolution of neoplastic cells together with the adjacent microenvironment. Steps of malignant progression including primary tumor outgrowth, therapeutic resistance, and distant metastasis are not determined solely by genetic alterations in ovarian cancer cells, but considerably shaped by the fitness advantage conferred by benign components in the ovarian stroma. As the dynamic cancer topography varies drastically during disease progression, heterologous cell types within the tumor microenvironment (TME) can actively determine the pathological track of ovarian cancer. Resembling many other solid tumor types, ovarian malignancy is nurtured by a TME whose dark side may have been overlooked, rather than overestimated. Further, harnessing breakthrough and targeting cures in human ovarian cancer requires insightful understanding of the merits and drawbacks of current treatment modalities, which mainly target transformed cells. Thus, designing novel and precise strategies that both eliminate cancer cells and manipulate the TME is increasingly recognized as a rational avenue to improve therapeutic outcome and prevent disease deterioration of ovarian cancer patients.
ovarian cancer / stromal cells / tumor microenvironment / therapeutic resistance / ectopic metastasis / combinational treatment / patient stratification
[1] |
Abrahams VM, Straszewski SL, Kamsteeg M, Hanczaruk B, Schwartz PE, Rutherford TJ, Mor G (2003) Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res 63:5573–5581
|
[2] |
Ackerman D, Simon MC (2014) Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment. Trends Cell Biol 24:472–478
CrossRef
Google scholar
|
[3] |
Agarwal A, Tressel SL, Kaimal R, Balla M, Lam FH, Covic L, Kuliopulos A (2010) Identification of a metalloprotease-chemokine signaling system in the ovarian cancer microenvironment: implications for antiangiogenic therapy. Cancer Res 70:5880–5890
CrossRef
Google scholar
|
[4] |
Aiello NM, Brabletz T, Kang Y, Nieto MA, Weinberg RA, Stanger BZ (2017) Upholding a role for EMT in pancreatic cancer metastasis. Nature 547:E7–E8
CrossRef
Google scholar
|
[5] |
Alexander ET, Minton AR, Peters MC, van Ryn J, Gilmour SK (2016) Thrombin inhibition and cisplatin block tumor progression in ovarian cancer by alleviating the immunosuppressive microenvironment. Oncotarget 7:85291–85305
CrossRef
Google scholar
|
[6] |
Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F, Olimpio CO, Bonardi C, Garbi A, Lissoni A
CrossRef
Google scholar
|
[7] |
Alvero AB, Montagna MK, Craveiro V, Liu LZ, Mor G (2012) Distinct subpopulations of epithelial ovarian cancer cells can differentially induce macrophages and T regulatory cells toward a pro-tumor phenotype. Am J Reprod Immunol 67:256–265
CrossRef
Google scholar
|
[8] |
Au Yeung CL, Co NN, Tsuruga T, Yeung TL, Kwan SY, Leung CS, Li Y, Lu ES, Kwan K, Wong KK
CrossRef
Google scholar
|
[9] |
Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Bio 10:165–177
CrossRef
Google scholar
|
[10] |
Azmi AS, Bao B, Sarkar FH (2013) Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev 32:623–642
CrossRef
Google scholar
|
[11] |
Blanco LZ, Kuhn E, Morrison JC, Bahadirli-Talbott A, Smith-Sehdev A, Kurman RJ (2017) Steroid hormone synthesis by the ovarian stroma surrounding epithelial ovarian tumors: a potential mechanism in ovarian tumorigenesis. Mod Pathol 30:563–576
CrossRef
Google scholar
|
[12] |
Bohm S, Montfort A, Pearce OMT, Topping J, Chakravarty P, Everitt GLA, Clear A, McDermott JR, Ennis D, Dowe T
CrossRef
Google scholar
|
[13] |
Bravo-Sagua, R., Mattar, P., Diaz, X., Lavandero, S., Cifuentes, M. (2016). Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications. Front Physiol 7.
CrossRef
Google scholar
|
[14] |
Brunckhorst MK, Xu Y, Lu R, Yu Q (2014) Angiopoietins promote ovarian cancer progression by establishing a procancer microenvironment. Am J Pathol 184:2285–2296
CrossRef
Google scholar
|
[15] |
Budnik V, Ruiz-Canada C, Wendler F (2016) Extracellular vesicles round off communication in the nervous system. Nat Rev Neurosci 17:160–172
CrossRef
Google scholar
|
[16] |
Bussard KM, Mutkus L, Stumpf K, Gomez-Manzano C, Marini FC (2016) Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res 18:84
CrossRef
Google scholar
|
[17] |
Cai J, Tang H, Xu L, Wang X, Yang C, Ruan S, Guo J, Hu S, Wang Z (2012) Fibroblasts in omentum activated by tumor cells promote ovarian cancer growth, adhesion and invasiveness. Carcinogenesis 33:20–29
CrossRef
Google scholar
|
[18] |
Carbotti G, Orengo AM, Mezzanzanica D, Bagnoli M, Brizzolara A, Emionite L, Puppo A, Centurioni MG, Bruzzone M, Marroni P
CrossRef
Google scholar
|
[19] |
Cardenas C, Montagna MK, Pitruzzello M, Lima E, Mor G, Alvero AB (2017) Adipocyte microenvironment promotes Bcl(xl) expression and confers chemoresistance in ovarian cancer cells. Apoptosis 22:558–569
CrossRef
Google scholar
|
[20] |
Carroll MJ, Kapur A, Felder M, Patankar MS, Kreeger PK (2016) M2 macrophages induce ovarian cancer cell proliferation via a heparin binding epidermal growth factor/matrix metalloproteinase 9 intercellular feedback loop. Oncotarget 7:86608–86620
CrossRef
Google scholar
|
[21] |
Chang DK, Peterson E, Sun J, Goudie C, Drapkin RI, Liu JF, Matulonis U, Zhu Q, Marasco WA (2016) Anti-CCR4 monoclonal antibody enhances antitumor immunity by modulating tumorinfiltrating Tregs in an ovarian cancer xenograft humanized mouse model. Oncoimmunology 5:e1090075
CrossRef
Google scholar
|
[22] |
Chen F, Zhuang X, Lin L, Yu P, Wang Y, Shi Y, Hu G, Sun Y (2015) New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med 13:278
CrossRef
Google scholar
|
[23] |
Chen, X., Ying, X., Wang, X., Wu, X., Zhu, Q., and Wang, X. (2017). Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization. Oncol Rep.
CrossRef
Google scholar
|
[24] |
Cho JA, Park H, Lim EH, Kim KH, Choi JS, Lee JH, Shin JW, Lee KW (2011) Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts. Gynecol Oncol 123:379–386
CrossRef
Google scholar
|
[25] |
Choi PW, Ng SW (2017) The functions of MicroRNA-200 family in ovarian cancer: beyond epithelial-mesenchymal transition. Int J Mol Sci 18:1207
CrossRef
Google scholar
|
[26] |
Choi JH, Lee KT, Leung PCK (2011) Estrogen receptor alpha pathway is involved in leptin-induced ovarian cancer cell growth. Carcinogenesis 32:589–596
CrossRef
Google scholar
|
[27] |
Clark R, Krishnan V, Schoof M, Rodriguez I, Theriault B, Chekmareva M, Rinker-Schaeffert C (2013) Milky spots promote ovarian cancer metastatic colonization of peritoneal adipose in experimental models. Am J Pathol 183:576–591
CrossRef
Google scholar
|
[28] |
Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL, Tomchuck SL, Honer zu Bentrup K, Danka ES, Henkle SL, Scandurro AB (2009) The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci USA 106:3806–3811
CrossRef
Google scholar
|
[29] |
Condamine T, Ramachandran I, Youn JI, Gabrilovich DI (2015) Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu Rev Med 66:97–110
CrossRef
Google scholar
|
[30] |
Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6:2853–2868
CrossRef
Google scholar
|
[31] |
Courtwright A, Siamakpour-Reihani S, Arbiser JL, Banet N, Hilliard E, Fried L, Livasy C, Ketelsen D, Nepal DB, Perou CM
CrossRef
Google scholar
|
[32] |
Crow J, Atay S, Banskota S, Artale B, Schmitt S, Godwin AK (2017) Exosomes as mediators of platinum resistance in ovarian cancer. Oncotarget 8:11917–11936
CrossRef
Google scholar
|
[33] |
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M
CrossRef
Google scholar
|
[34] |
da Silva RF, Yoshida A, Cardozo DM, Jales RM, Paust S, Derchain S, Guimarães F (2017) Natural killer cells response to IL-2 stimulation is distinct between ascites with the presence or absence of malignant cells in ovarian cancer patients. Int J Mol Sci 18:E856
CrossRef
Google scholar
|
[35] |
Deng WM, Gu X, Lu Y, Gu C, Zheng YY, Zhang ZS, Chen L, Yao Z, Li LY (2012) Down-modulation of TNFSF15 in ovarian cancer by VEGF and MCP-1 is a pre-requisite for tumor neovascularization. Angiogenesis 15:71–85
CrossRef
Google scholar
|
[36] |
Dhawan U, Wang SM, Chu YH, Huang GS, Lin YR, Hung YC, Chen WL (2016) Nanochips of tantalum oxide nanodots as artificialmicroenvironments for monitoring Ovarian cancer progressiveness. Sci Rep 6:31998
CrossRef
Google scholar
|
[37] |
Ding DC, Liu HW, Chu TY (2016) Interleukin-6 from ovarian mesenchymal stem cells promotes proliferation, sphere and colony formation and tumorigenesis of an ovarian cancer cell line SKOV3. J Cancer 7:1815–1823
CrossRef
Google scholar
|
[38] |
Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S
CrossRef
Google scholar
|
[39] |
Duluc D, Delneste Y, Tan F, Moles MP, Grimaud L, Lenoir J, Preisser L, Anegon I, Catala L, Ifrah N
CrossRef
Google scholar
|
[40] |
Duluc D, Corvaisier M, Blanchard S, Catala L, Descamps P, Gamelin E, Ponsoda S, Delneste Y, Hebbar M, Jeannin P (2009) Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumorassociated macrophages. Int J Cancer 125:367–373
CrossRef
Google scholar
|
[41] |
Felices M, Chu S, Kodal B, Bendzick L, Ryan C, Lenvik AJ, Boylan KLM, Wong HC, Skubitz APN, Miller JS, Geller MA (2017) IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. Gynecol Oncol 145:453–461
CrossRef
Google scholar
|
[42] |
Finkernagel F, Reinartz S, Lieber S, Adhikary T, Wortmann A, Hoffmann N, Bieringer T, Nist A, Stiewe T, Jansen JM
CrossRef
Google scholar
|
[43] |
Geis AL, Fan H, Wu X, Wu S, Huso DL, Wolfe JL, Sears CL, Pardoll DM, Housseau F (2015) Regulatory T-cell response to enterotoxigenic Bacteroides fragilis colonization triggers IL17-dependent colon carcinogenesis. Cancer Dis 5:1098–1109
CrossRef
Google scholar
|
[44] |
Gobbo, J., Marcion, G., Cordonnier, M., Dias, A. M. M., Pernet, N., Hammann, A., Richaud, S., Mjahed, H., Isambert, N., Clausse, V.,
CrossRef
Google scholar
|
[45] |
Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA (2004) Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res 64:7045–7049
CrossRef
Google scholar
|
[46] |
Guaita-Esteruelas, S., Guma, J., Masana, L., and Borras, J. (2017). The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5. Mol Cell Endocrinol.
|
[47] |
Gusky HC, Diedrich J, MacDougald OA, Podgorski I (2016) Omentum and bone marrow: how adipocyte-rich organs create tumour microenvironments conducive for metastatic progression. Obes Rev 17:1015–1029
CrossRef
Google scholar
|
[48] |
Gutwein P, Stoeck A, Riedle S, Gast D, Runz S, Condon TP, Marme A, Phong MC, Linderkamp O, Skorokhod A, Altevogt P (2005) Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells. Clin Cancer Res 11:2492–2501
CrossRef
Google scholar
|
[49] |
Hagemann T, Wilson J, Burke F, Kulbe H, Li NF, Pluddemann A, Charles K, Gordon S, Balkwill FR (2006) Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J Immunol 176:5023–5032
CrossRef
Google scholar
|
[50] |
Han L, Xu J, Xu Q, Zhang B, Lam EW, Sun Y (2017). Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies. Med Res Rev.
CrossRef
Google scholar
|
[51] |
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
CrossRef
Google scholar
|
[52] |
Harjes U, Bridges E, Gharpure KM, Roxanis I, Sheldon H, Miranda F, Mangala LS, Pradeep S, Lopez-Berestein G, Ahmed A
CrossRef
Google scholar
|
[53] |
Hart KM, Byrne KT, Molloy MJ, Usherwood EM, Berwin B (2011) IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer. Front Immunol 2:29
CrossRef
Google scholar
|
[54] |
Heindl A, Lan C, Rodrigues DN, Koelble K, Yuan Y (2016) Similarity and diversity of the tumor microenvironment in multiple metastases: critical implications for overall and progression-free survival of high-grade serous ovarian cancer. Oncotarget 7:71123–71135
CrossRef
Google scholar
|
[55] |
Hu W, Wang J, He X, Zhang H, Yu F, Jiang L, Chen D, Chen J, Dou J (2011) Human umbilical blood mononuclear cell-derived mesenchymal stem cells serve as interleukin-21 gene delivery vehicles for epithelial ovarian cancer therapy in nude mice. Biotechnol Appl Biochem 58:397–404
CrossRef
Google scholar
|
[56] |
Huang S, Van Arsdall M, Tedjarati S, McCarty M, Wu W, Langley R, Fidler IJ (2002) Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst 94:1134–1142
CrossRef
Google scholar
|
[57] |
Huijbers EJM, van Beijnum JR, Thijssen VL, Sabrkhany S, Nowak-Sliwinska P, Griffioen AW (2016) Role of the tumor stroma in resistance to anti-angiogenic therapy. Drug Resist Update 25:26–37
CrossRef
Google scholar
|
[58] |
Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H
CrossRef
Google scholar
|
[59] |
Jiang J, Chen W, Zhuang R, Song T, Li P (2010) The effect of endostatin mediated by human mesenchymal stem cells on ovarian cancer cells in vitro. J Cancer Res Clin Oncol 136:873–881
CrossRef
Google scholar
|
[60] |
Josephs DH, Bax HJ, Dodev T, Georgouli M, Nakamura M, Pellizzari G, Saul L, Karagiannis P, Cheung A, Herraiz C
CrossRef
Google scholar
|
[61] |
Kanlikilicer P, Rashed MH, Bayraktar R, Mitra R, Ivan C, Aslan B, Zhang X, Filant J, Silva AM, Rodriguez-Aguayo C
CrossRef
Google scholar
|
[62] |
Karnezis AN, Cho KR, Gilks CB, Pearce CL, Huntsman DG (2017) The disparate origins of ovarian cancers: pathogenesis and prevention strategies. Nat Rev Cancer 17:65–74
CrossRef
Google scholar
|
[63] |
Ke X, Zhang S, Wu M, Lou J, Zhang J, Xu T, Huang L, Huang P, Wang F, Pan S (2016) Tumor-associated macrophages promote invasion via Toll-like receptors signaling in patients with ovarian cancer. Int Immunopharmacol 40:184–195
CrossRef
Google scholar
|
[64] |
Kelleher RJ Jr, Balu-Iyer S, Loyall J, Sacca AJ, Shenoy GN, Peng P, Iyer V, Fathallah AM, Berenson CS, Wallace PK
CrossRef
Google scholar
|
[65] |
Kipps E, Tan DS, Kaye SB (2013) Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research. Nat Rev Cancer 13:273–282
CrossRef
Google scholar
|
[66] |
Klemm F, Joyce JA (2015) Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol 25:198–213
CrossRef
Google scholar
|
[67] |
Kobayashi H, Iwai K, Niiro E, Morioka S, Yamada Y, Ogawa K, Kawahara N (2017) The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer. Biomed Rep 7:209–213
CrossRef
Google scholar
|
[68] |
Komdeur FL, Wouters MCA, Workel HH, Tijans AM, Terwindt ALJ, Brunekreeft KL, Plat A, Klip HG, Eggink FA, Leffers N
CrossRef
Google scholar
|
[69] |
Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT (2010) Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330:827–830
CrossRef
Google scholar
|
[70] |
Krockenberger M, Dombrowski Y, Weidler C, Ossadnik M, Honig A, Hausler S, Voigt H, Becker JC, Leng L, Steinle A
CrossRef
Google scholar
|
[71] |
Kuerti S, Oliveira-Ferrer L, Milde-Langosch K, Schmalfeldt B, Legler K, Woelber L, Prieske K, Mahner S, Trillsch F (2017) VEGF-C expression attributes the risk for lymphatic metastases to ovarian cancer patients. Oncotarget 8:43218
CrossRef
Google scholar
|
[72] |
Labiche A, Heutte N, Herlin P, Chasle J, Gauduchon P, Elie N (2010) Stromal compartment as a survival prognostic factor in advanced ovarian carcinoma. Int J Gynecol Cancer 20:28–33
CrossRef
Google scholar
|
[73] |
Landskron J, Helland O, Torgersen KM, Aandahl EM, Gjertsen BT, Bjorge L, Tasken K (2015) Activated regulatory and memory T-cells accumulate in malignant ascites from ovarian carcinoma patients. Cancer Immunol Immunother 64:337–347
CrossRef
Google scholar
|
[74] |
Latifi A, Abubaker K, Castrechini N, Ward AC, Liongue C, Dobill F, Kumar J, Thompson EW, Quinn MA, Findlay JK, Ahmed N (2011) Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem celllike profile. J Cell Biochem 112:2850–2864
CrossRef
Google scholar
|
[75] |
Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177:1053–1064
CrossRef
Google scholar
|
[76] |
Linnerth-Petrik NM, Santry LA, Moorehead R, Jucker M, Wootton SK, Petrik J (2016) Akt isoform specific effects in ovarian cancer progression. Oncotarget 7:74820–74833
CrossRef
Google scholar
|
[77] |
Liu YY, Metzinger MN, Lewellen KA, Cripps SN, Carey KD, Harper EI, Shi ZG, Tarwater L, Grisoli A, Lee E
CrossRef
Google scholar
|
[78] |
Lu X, Horner JW, Paul E, Shang X, Troncoso P, Deng P, Jiang S, Chang Q, Spring DJ, Sharma P
CrossRef
Google scholar
|
[79] |
Martinet L, Poupot R, Mirshahi P, Rafii A, Fournie JJ, Mirshahi M, Poupot M (2010) Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses. Int J Cancer 126:2143–2152
CrossRef
Google scholar
|
[80] |
McDaniel AS, Stall JN, Hovelson DH, Cani AK, Liu CJ, Tomlins SA, Cho KR (2015) Next-generation sequencing of tubal intraepithelial carcinomas. JAMA Oncol 1:1128–1132
CrossRef
Google scholar
|
[81] |
McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, Cabrera L, Keller E, McCauley L, Cho KR, Buckanovich RJ (2011) Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Investig 121:3206–3219
CrossRef
Google scholar
|
[82] |
Mikula-Pietrasik J, Uruski P, Sosinska P, Maksin K, Piotrowska-Kempisty H, Kucinska M, Murias M, Szubert S, Wozniak A, Szpurek D
CrossRef
Google scholar
|
[83] |
Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB,Watson PH, Nelson BH (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLos ONE 4:e6412
CrossRef
Google scholar
|
[84] |
Miranda F, Ahmed AA (2017) How to make ovarian cancer cells “sick-too”. Cell Cycle 16:15–16
CrossRef
Google scholar
|
[85] |
Miranda F, Mannion D, Liu S, Zheng Y, Mangala LS, Redondo C, Herrero-Gonzalez S, Xu R, Taylor C, Chedom DF
CrossRef
Google scholar
|
[86] |
Mukherjee S, Pal M, Mukhopadhyay S, Das I, Hazra R, Ghosh S,Mondal RK, Bal R (2017). VEGF expression to support targeted therapy in ovarian surface epithelial neoplasms. J Clin Diagn Res 11: EC43–EC46.
CrossRef
Google scholar
|
[87] |
Musrap N, Diamandis EP (2012) Revisiting the complexity of the ovarian cancer microenvironment-clinical implications for treatment strategies. Mol Cancer Res 10:1254–1264
CrossRef
Google scholar
|
[88] |
Nakamura K, Sawada K, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T (2016) Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer 15:48
CrossRef
Google scholar
|
[89] |
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS
CrossRef
Google scholar
|
[90] |
Nieman KM, Romero IL, Van Houten B, Lengyel E (2013) Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta 1831:1533–1541
CrossRef
Google scholar
|
[91] |
Noskova V, Ahmadi S, Asander E, Casslen B (2009) Ovarian cancer cells stimulate uPA gene expression in fibroblastic stromal cells via multiple paracrine and autocrine mechanisms. Gynecol Oncol 115:121–126
CrossRef
Google scholar
|
[92] |
Obermajer N, Muthuswamy R, Odunsi K, Edwards RP, Kalinski P (2011) PGE(2)-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res 71:7463–7470
CrossRef
Google scholar
|
[93] |
Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D
CrossRef
Google scholar
|
[94] |
Pesce S, Tabellini G, Cantoni C, Patrizi O, Coltrini D, Rampinelli F, Matta J, Vivier E, Moretta A, Parolini S, Marcenaro E (2015) B7-H6-mediated downregulation of NKp30 in NK cells contributes to ovarian carcinoma immune escape. Oncoimmunology 4: e1001224
CrossRef
Google scholar
|
[95] |
Pink RC, Samuel P, Massa D, Caley DP, Brooks SA, Carter DRF (2015) The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecol Oncol 137:143–151
CrossRef
Google scholar
|
[96] |
Pogge von Strandmann E, Reinartz S, Wager U, Müller R (2017) Tumor-host cell interactions in ovarian cancer: pathways to therapy failure. Trends Cancer 3:137–148
CrossRef
Google scholar
|
[97] |
Rabban JT, Vohra P, Zaloudek CJ (2015) Nongynecologic metastases to fallopian tube mucosa: a potential mimic of tubal highgrade serous carcinoma and benign tubal mucinous metaplasia or nonmucinous hyperplasia. Am J Surg Pathol 39:35–51
CrossRef
Google scholar
|
[98] |
Reinartz S, Finkernagel F, Adhikary T, Rohnalter V, Schumann T, Schober Y, Nockher WA, Nist A, Stiewe T, Jansen JM
CrossRef
Google scholar
|
[99] |
Runz S, Keller S, Rupp C, Stoeck A, Issa Y, Koensgen D, Mustea A, Sehouli J, Kristiansen G, Altevogt P (2007) Malignant ascitesderived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol 107:563–571
CrossRef
Google scholar
|
[100] |
Saharinen P, Eklund L, Pulkki K, Bono P, Alitalo K (2011) VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med 17:347–362
CrossRef
Google scholar
|
[101] |
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C
CrossRef
Google scholar
|
[102] |
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C
CrossRef
Google scholar
|
[103] |
Schauer IG, Sood AK, Mok S, Liu JS (2011) Cancer-associated fibroblasts and their putative role in potentiating the initiation and development of epithelial ovarian cancer. Neoplasia 13:393–405
CrossRef
Google scholar
|
[104] |
Schmidt BA, Horsley V (2013) Intradermal adipocytes mediate fibroblast recruitment during skin wound healing. Development 140:1517–1527
CrossRef
Google scholar
|
[105] |
Scully RE, Richardson GS (1961) Luteinization of the stroma of metastatic cancer involving the ovary and its endocrine significance. Cancer 14:827–840
CrossRef
Google scholar
|
[106] |
Sheng X, Mittelman SD (2014) The role of adipose tissue and obesity in causing treatment resistance of acute lymphoblastic leukemia. Frontiers Pediatr 2:53
CrossRef
Google scholar
|
[107] |
Siamakpour-Reihani S, Caster J, Bandhu Nepal D, Courtwright A, Hilliard E, Usary J, Ketelsen D, Darr D, Shen XJ, Patterson C, Klauber-Demore N (2011) The role of calcineurin/NFAT in SFRP2 induced angiogenesis–a rationale for breast cancer treatment with the calcineurin inhibitor tacrolimus. PLos ONE 6:e20412
CrossRef
Google scholar
|
[108] |
Simpson S (2007) Trabectedin too toxic in ovarian cancer? Lancet Oncol 8:1061
CrossRef
Google scholar
|
[109] |
Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, Andreeff M, Marini F (2009) Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLos ONE 4:e4992
CrossRef
Google scholar
|
[110] |
Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du JY, Davis A, Mongare MM, Gould J, Frederick DT
CrossRef
Google scholar
|
[111] |
Sun Y (2015) Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures. Med Res Rev 35:408–436
CrossRef
Google scholar
|
[112] |
Sun Y, Campisi J, Higano C, Beer TM, Porter P, Coleman I, True L, Nelson PS (2012) Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat Med 18:1359–1368
CrossRef
Google scholar
|
[113] |
Sun Y, Zhu D, Chen F, Qian M, Wei H, Chen W, Xu J (2016) SFRP2 augments WNT16B signaling to promote therapeutic resistance in the damaged tumor microenvironment. Oncogene 35:4321–4334
CrossRef
Google scholar
|
[114] |
Tajan M, Vousden KH (2016) The quid pro quo of the tumor/stromal interaction. Cell Metab 24:645–646
CrossRef
Google scholar
|
[115] |
Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumorderived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21
CrossRef
Google scholar
|
[116] |
Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, Khosla S, Jensen MD, Kirkland JL (2010) Fat tissue, aging, and cellular senescence.Aging Cell 9:667–684
CrossRef
Google scholar
|
[117] |
Toro L, Bohovic R, Matuskova M, Smolkova B, Kucerova L (2016) Metastatic ovarian cancer can be efficiently treated by genetically modified mesenchymal stromal cells. Stem Cells Dev 25:1640–1651
CrossRef
Google scholar
|
[118] |
Tucker SL, Gharpure K, Herbrich SM, Unruh AK, Nick AM, Crane EK, Coleman RL, Guenthoer J, Dalton HJ, Wu SY
CrossRef
Google scholar
|
[119] |
Walter M, Liang S, Ghosh S, Hornsby PJ, Li R (2009) Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene 28:2745–2755
CrossRef
Google scholar
|
[120] |
Wang R, Zhang T, Ma Z, Wang Y, Cheng Z, Xu H, Li W, Wang X (2010) The interaction of coagulation factor XII and monocyte/macrophages mediating peritoneal metastasis of epithelial ovarian cancer. Gynecol Oncol 117:460–466
CrossRef
Google scholar
|
[121] |
Wang WM, Kryczek I, Dostal L, Lin H, Tan LJ, Zhao LL, Lu FJ, Wei S, Maj T, Peng DJ
CrossRef
Google scholar
|
[122] |
Webb JR, Milne K, Watson P, deLeeuw RJ, Nelson BH (2014) Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. Clin Cancer Res 20:434–444
CrossRef
Google scholar
|
[123] |
Weiner-Gorzel K, Dempsey E, Milewska M, McGoldrick A, Toh V, Walsh A, Lindsay S, Gubbins L, Cannon A, Sharpe D
CrossRef
Google scholar
|
[124] |
Wilson TR, Fridlyand J, Yan YB, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang YL, Sosman J
CrossRef
Google scholar
|
[125] |
Wong JL, Berk E, Edwards RP, Kalinski P (2013) IL-18-primed helper NK cells collaborate with dendritic cells to promote recruitment of effector CD8+ T cells to the tumor microenvironment. Cancer Res 73:4653–4662
CrossRef
Google scholar
|
[126] |
Worzfeld T, Pogge von Strandmann E, Huber M, Adhikary T, Wagner U, Reinartz S, Muller R (2017) The unique molecular and cellular microenvironment of ovarian cancer. Front Oncol 7:24
CrossRef
Google scholar
|
[127] |
Wu M, Chen X, Lou JF, Zhang SP, Zhang XJ, Huang L, Sun RH, Huang PJ, Wang F, Pan SY (2016a) TGF-beta 1 contributes to CD8(+) Treg induction through p38 MAPK signaling in ovarian cancer microenvironment. Oncotarget 7:44534–44544
|
[128] |
Wu M, Lou J, Zhang S, Chen X, Huang L, Sun R, Huang P, Pan S, Wang F (2016b) Gene expression profiling of CD8+ T cells induced by ovarian cancer cells suggests a possible mechanism for CD8+ Treg cell production. Cell Prolif 49:669–677
CrossRef
Google scholar
|
[129] |
Wu M, Chen X, Lou J, Zhang S, Zhang X, Huang L, Sun R, Huang P, Pan S, Wang F (2017a) Changes in regulatory T cells in patients with ovarian cancer undergoing surgery: preliminary results. Int Immunopharmacol 47:244–250
CrossRef
Google scholar
|
[130] |
Wu Q, Wu X, Ying X, Zhu Q, Wang X, Jiang L, Chen X, Wu Y, Wang X (2017b) Suppression of endothelial cell migration by tumor associated macrophage-derived exosomes is reversed by epithelial ovarian cancer exosomal lncRNA. Cancer Cell Int 17:62
CrossRef
Google scholar
|
[131] |
Yang L, Achreja A, Yeung TL, Mangala LS, Jiang D, Han C, Baddour J, Marini JC, Ni J, Nakahara R
CrossRef
Google scholar
|
[132] |
Yin J, Yan XD, Yao X, Zhang YL, Shan Y, Mao N, Yang YL, Pan LY (2012) Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients. J Cell Mol Med 16:337–348
CrossRef
Google scholar
|
[133] |
Yokoi A, Yoshioka Y, Yamamoto Y, Ishikawa M, Ikeda SI, Kato T, Kiyono T, Takeshita F, Kajiyama H, Kikkawa F, Ochiya T (2017) Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer. Nat Commun 8:14470
CrossRef
Google scholar
|
[134] |
Yoshida M, Taguchi A, Kawana K, Adachi K, Kawata A, Ogishima J, Nakamura H, Fujimoto A, Sato M, Inoue T
CrossRef
Google scholar
|
[135] |
Young RH (2006) From krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the krukenberg tumor. Adv Anat Pathol 13:205–227
CrossRef
Google scholar
|
[136] |
Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN
CrossRef
Google scholar
|
[137] |
Zhang T, Ma Z, Wang R, Wang Y, Wang S, Cheng Z, Xu H, Jin X, Li W, Wang X (2010) Thrombin facilitates invasion of ovarian cancer along peritoneum by inducing monocyte differentiation toward tumor-associated macrophage-like cells. Cancer Immunol Immunother 59:1097–1108
CrossRef
Google scholar
|
[138] |
Zhang Y, Tang H, Cai J, Zhang T, Guo J, Feng D, Wang Z (2011) Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett 303:47–55
CrossRef
Google scholar
|
[139] |
Zhang YL, Dong WH, Wang JJ, Cai J, Wang ZH (2017) Human omental adipose-derived mesenchymal stem cell-conditioned medium alters the proteomic profile of epithelial ovarian cancer cell lines in vitro. Oncotargets Ther 10:1655–1663
CrossRef
Google scholar
|
[140] |
Zhou Y, Xu Y, Chen LJ, Xu B, Wu CP, Jiang JT (2015) B7-H6 expression correlates with cancer progression and patient’s survival in human ovarian cancer. Int J Clin Exp Pathol 8:9428–9433
|
[141] |
Zhu QY, Wu XL, Wu YQ, Wang XP (2016) Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer. Oncol Rep 36:3472–3478
CrossRef
Google scholar
|
/
〈 | 〉 |