Ovarian tumor microenvironment contributes to tumor progression and chemoresistance

Adriana Ponton-Almodovar , Samuel Sanderson , Ramandeep Rattan , Jamie J. Bernard , Sachi Horibata

Cancer Drug Resistance ›› 2024, Vol. 7 : 53

PDF
Cancer Drug Resistance ›› 2024, Vol. 7 :53 DOI: 10.20517/cdr.2024.111
review-article

Ovarian tumor microenvironment contributes to tumor progression and chemoresistance

Author information +
History +
PDF

Abstract

Ovarian cancer is one of the deadliest gynecologic cancers affecting the female reproductive tract. This is largely attributed to frequent recurrence and development of resistance to the platinum-based drugs cisplatin and carboplatin. One of the major contributing factors to increased cancer progression and resistance to chemotherapy is the tumor microenvironment (TME). Extracellular signaling from cells within the microenvironment heavily influences progression and drug resistance in ovarian cancer. This is frequently done through metabolic reprogramming, the process where cancer cells switch between biochemical pathways to increase their chances of survival and proliferation. Here, we focus on how crosstalk between components of the TME and the tumor promotes resistance to platinum-based chemotherapy. We highlight the role of cancer-associated fibroblasts, immune cells, adipocytes, and endothelial cells in ovarian tumor progression, invasion, metastasis, and chemoresistance. We also highlight recent advancements in targeting components of the TME as a novel therapeutic avenue to combat chemoresistance in ovarian cancer.

Keywords

Ovarian cancer / chemoresistance / tumor microenvironment

Cite this article

Download citation ▾
Adriana Ponton-Almodovar, Samuel Sanderson, Ramandeep Rattan, Jamie J. Bernard, Sachi Horibata. Ovarian tumor microenvironment contributes to tumor progression and chemoresistance. Cancer Drug Resistance, 2024, 7: 53 DOI:10.20517/cdr.2024.111

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Siegel RL,Jemal A.Cancer statistics, 2024.CA Cancer J Clin2024;74:12-49

[2]

du Bois A, Lück HJ, Meier W, et al; Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003;95:1320-9.

[3]

Moore K,Scambia G.Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer.N Engl J Med2018;379:2495-505

[4]

Ray-Coquard I, Pautier P, Pignata S, et al; PAOLA-1 Investigators. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 2019;381:2416-28.

[5]

González-Martín A, Pothuri B, Vergote I, et al; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2019;381:2391-402.

[6]

Gottesman MM,Bates SE.Multidrug resistance in cancer: role of ATP-dependent transporters.Nat Rev Cancer2002;2:48-58

[7]

Masuda H,Lai GM,Rothenberg M.Increased DNA repair as a mechanism of acquired resistance to cis-diamminedichloroplatinum (II) in human ovarian cancer cell lines.Cancer Res1988;48:5713-6

[8]

Patel RP,Yin D.Cross-resistance of cisplatin selected cells to anti-microtubule agents: role of general survival mechanisms.Transl Oncol2021;14:100917 PMCID:PMC7586247

[9]

Ortiz M,Mitchell K.Mechanisms of chemotherapy resistance in ovarian cancer.Cancer Drug Resist2022;5:304-16 PMCID:PMC9255249

[10]

Demicco M,Leithner K.Metabolic heterogeneity in cancer.Nat Metab2024;6:18-38

[11]

Navarro C,Santeliz R.Metabolic reprogramming in cancer cells: emerging molecular mechanisms and novel therapeutic approaches.Pharmaceutics2022;14:1303 PMCID:PMC9227908

[12]

Hanahan D.Hallmarks of cancer: new dimensions.Cancer Discov2022;12:31-46

[13]

Yoo HC,Sung Y.Glutamine reliance in cell metabolism.Exp Mol Med2020;52:1496-516 PMCID:PMC8080614

[14]

Hanahan D.Hallmarks of cancer: the next generation.Cell2011;144:646-74

[15]

Altman BJ,Dang CV.From Krebs to clinic: glutamine metabolism to cancer therapy.Nat Rev Cancer2016;16:773

[16]

Godwin AK,O'Dwyer PJ,Hamilton TC.High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis.Proc Natl Acad Sci U S A1992;89:3070-4 PMCID:PMC48805

[17]

Guo J,Tabata S,Tomita M.Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells.BMC Cancer2021;21:174 PMCID:PMC7891143

[18]

Hudson CD,Nagaraj AB.Altered glutamine metabolism in platinum resistant ovarian cancer.Oncotarget2016;7:41637-49 PMCID:PMC5173084

[19]

Ahmed N,Leung D,Kannourakis G.Tumour microenvironment and metabolic plasticity in cancer and cancer stem cells: perspectives on metabolic and immune regulatory signatures in chemoresistant ovarian cancer stem cells.Semin Cancer Biol2018;53:265-81

[20]

Yang Y,Yang J,Wei X.Tumor microenvironment in ovarian cancer: function and therapeutic strategy.Front Cell Dev Biol2020;8:758 PMCID:PMC7431690

[21]

Jiang Y,Zhou S.Targeting tumor microenvironment in ovarian cancer: premise and promise.Biochim Biophys Acta Rev Cancer2020;1873:188361

[22]

Yeldag G,Del Río Hernández A.Chemoresistance and the self-maintaining tumor microenvironment.Cancers2018;10:471 PMCID:PMC6315745

[23]

Zhao L,Le X.Long noncoding RNA LINC00092 acts in cancer-associated fibroblasts to drive glycolysis and progression of ovarian cancer.Cancer Res2017;77:1369-82

[24]

Sun L,Yin M.Extracellular vesicle-encapsulated microRNA-296-3p from cancer-associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways.Cancer Sci2024;115:155-69 PMCID:PMC10823290

[25]

Zhou B,Li N.Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways.Int J Oncol2016;48:2087-97

[26]

Guo H,Dong H,Ma Y.Cancer-associated fibroblast-derived exosomal microRNA-98-5p promotes cisplatin resistance in ovarian cancer by targeting CDKN1A.Cancer Cell Int2019;19:347 PMCID:PMC6925473

[27]

Liu J,Ma Y.STING inhibitors sensitize platinum chemotherapy in ovarian cancer by inhibiting the CGAS-STING pathway in cancer-associated fibroblasts (CAFs).Cancer Lett2024;588:216700

[28]

Fang Y,Wang J.Cancer associated fibroblasts serve as an ovarian cancer stem cell niche through noncanonical Wnt5a signaling.NPJ Precis Oncol2024;8:7 PMCID:PMC10774407

[29]

Dai JM,Li C.Cancer-associated fibroblasts contribute to cancer metastasis and apoptosis resistance in human ovarian cancer via paracrine SDF-1α.Clin Transl Oncol2023;25:1606-16

[30]

Mukherjee S,Mehrotra M,Rekhi B.Homo and heterotypic cellular cross-talk in epithelial ovarian cancer impart pro-tumorigenic properties through differential activation of the Notch3 pathway.Cancers2022;14:3365 PMCID:PMC10887060

[31]

Hong L,Zheng L,Zhu G.Tumor-associated macrophages promote cisplatin resistance in ovarian cancer cells by enhancing WTAP-mediated N6-methyladenosine RNA methylation via the CXCL16/CXCR6 axis.Cancer Chemother Pharmacol2023;92:71-81 PMCID:PMC10261262

[32]

Chen C,Ruan Z.GATA3 encapsulated by tumor-associated macrophage-derived extracellular vesicles promotes immune escape and chemotherapy resistance of ovarian cancer cells by upregulating the CD24/Siglec-10 axis.Mol Pharm2023;20:971-86

[33]

Zhang X,Liu N.Molecular mechanism of CD163+ tumor-associated macrophage (TAM)-derived exosome-induced cisplatin resistance in ovarian cancer ascites.Ann Transl Med2022;10:1014 PMCID:PMC9577761

[34]

Ma J,Chen X.Ojeok-san enhances platinum sensitivity in ovarian cancer by regulating adipocyte paracrine IGF1 secretion.Adipocyte2024;13:2282566 PMCID:PMC10761029

[35]

Kim B.Impact of obesity and lysosomal dysfunction on chemoresistance in ovarian cancer.Biomedicines2024;12:604 PMCID:PMC10967917

[36]

Lin CN,Tsai HF.Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.J Biomed Sci2024;31:62 PMCID:PMC11167873

[37]

Rodriguez GM,McCloskey CW.The tumor microenvironment of epithelial ovarian cancer and its influence on response to immunotherapy.Cancers2018;10:242 PMCID:PMC6116043

[38]

Anderson NM.The tumor microenvironment.Curr Biol2020;30:R921-5 PMCID:PMC8194051

[39]

McEvoy LM,Spillane CD.Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer.BMC Cancer2015;15:547 PMCID:PMC4513971

[40]

Hoarau-Véchot J,Halabi N.Akt-activated endothelium promotes ovarian cancer proliferation through notch activation.J Transl Med2019;17:194 PMCID:PMC6558713

[41]

Yang D,Qian H.Cancer-associated fibroblasts: from basic science to anticancer therapy.Exp Mol Med2023;55:1322-32 PMCID:PMC10394065

[42]

Sahai E,Cukierman E.A framework for advancing our understanding of cancer-associated fibroblasts.Nat Rev Cancer2020;20:174-86 PMCID:PMC7046529

[43]

Liu ZL,Zheng LL,Shi L.Angiogenic signaling pathways and anti-angiogenic therapy for cancer.Signal Transduct Target Ther2023;8:198 PMCID:PMC10175505

[44]

Yoon H,Banerjee S.TGF-β1-mediated transition of resident fibroblasts to cancer-associated fibroblasts promotes cancer metastasis in gastrointestinal stromal tumor.Oncogenesis2021;10:13 PMCID:PMC7876107

[45]

Wright K,Kriet M,Thomas SM.Cancer-associated fibroblasts: master tumor microenvironment modifiers.Cancers2023;15:1899 PMCID:PMC10047485

[46]

Lv C,Yu Y.Wentilactone a reverses the NF-κB/ECM1 signaling-induced cisplatin resistance through inhibition of IKK/IκB in ovarian cancer cells.Nutrients2022;14:3790 PMCID:PMC9504226

[47]

Eckert MA,Xiao J,Lengyel E.The effects of chemotherapeutics on the ovarian cancer microenvironment.Cancers2021;13:3136 PMCID:PMC8268261

[48]

Schauer IG,Xing Z.Interleukin-1β promotes ovarian tumorigenesis through a p53/NF-κB-mediated inflammatory response in stromal fibroblasts.Neoplasia2013;15:409-20 PMCID:PMC3612913

[49]

Yeung TL,Wong KK.TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.Cancer Res2013;73:5016-28 PMCID:PMC3745588

[50]

You S,Xu Y,Song K.High expression of SLC7A1 in high-grade serous ovarian cancer promotes tumor progression and is involved in MAPK/ERK pathway and EMT.Cancer Med2024;13:e7217 PMCID:PMC11097251

[51]

Kalluri R.The biology, function, and biomedical applications of exosomes.Science2020;367:eaau6977 PMCID:PMC7717626

[52]

Lee S,Jin C.Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line.Gynecol Oncol2005;97:26-34

[53]

Han Z,Hong Z.Silencing of the STAT3 signaling pathway reverses the inherent and induced chemoresistance of human ovarian cancer cells.Biochem Biophys Res Commun2013;435:188-94

[54]

Chu L,Zhang W,Xu J.Periostin secreted by carcinoma-associated fibroblasts promotes ovarian cancer cell platinum resistance through the PI3K/Akt signaling pathway.Technol Cancer Res Treat2020;19:1533033820977535 PMCID:PMC7734496

[55]

Decout A,Venkatraman S.The cGAS-STING pathway as a therapeutic target in inflammatory diseases.Nat Rev Immunol2021;21:548-69 PMCID:PMC8029610

[56]

Mori Y,Sakai H.Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer.Cell Rep Med2024;5:101532 PMCID:PMC11149410

[57]

Wang X,Xu TM.HIF-1α is a rational target for future ovarian cancer therapies.Front Oncol2021;11:785111 PMCID:PMC8739787

[58]

Long F,Jia P,Jiang G.HIF-1α-induced autophagy contributes to cisplatin resistance in ovarian cancer cells.Pharmazie2018;73:533-6

[59]

Zhan T,Boutros M.Wnt signaling in cancer.Oncogene2017;36:1461-73 PMCID:PMC5357762

[60]

Zhang Z,Tang Z.Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer.J Transl Med2024;22:565 PMCID:PMC11170811

[61]

Doo DW,Londoño AI.Inhibition of the Wnt/β-catenin pathway enhances antitumor immunity in ovarian cancer.Ther Adv Med Oncol2020;12:1758835920913798 PMCID:PMC7158255

[62]

Cojoc M,Muders MH.A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms.Semin Cancer Biol2015;31:16-27

[63]

Piki E,Raivola J.ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity.Cell Death Discov2023;9:222 PMCID:PMC10317980

[64]

Zhang F,Gao HF.Cancer-associated fibroblasts induce epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer via CXCL12/CXCR4 axis.Future Oncol2020;16:2619-33

[65]

Mo W,Patel A.CXCR4/CXCL12 mediate autocrine cell- cycle progression in NF1-associated malignant peripheral nerve sheath tumors.Cell2013;152:1077-90 PMCID:PMC3594500

[66]

Xiu M,Li B.The role of notch3 signaling in cancer stemness and chemoresistance: molecular mechanisms and targeting strategies.Front Mol Biosci2021;8:694141 PMCID:PMC8237348

[67]

Ji Z,Gao W,Wang H.Cancer-associated fibroblast-derived interleukin-8 promotes ovarian cancer cell stemness and malignancy through the Notch3-mediated signaling.Front Cell Dev Biol2021;9:684505 PMCID:PMC8280773

[68]

Johnson RL,Thangavelu A,de Jong D.Barriers to immunotherapy in ovarian cancer: metabolic, genomic, and immune perturbations in the tumour microenvironment.Cancers2021;13:6231 PMCID:PMC8699358

[69]

Liu Y,Lewellen KA.Obesity contributes to ovarian cancer metastatic success through increased lipogenesis, enhanced vascularity, and decreased infiltration of M1 macrophages.Cancer Res2015;75:5046-57 PMCID:PMC4668203

[70]

Raudenska M,Fojtu M,Masarik M.Unexpected therapeutic effects of cisplatin.Metallomics2019;11:1182-99

[71]

Li H,Jiang X.CircITGB6 promotes ovarian cancer cisplatin resistance by resetting tumor-associated macrophage polarization toward the M2 phenotype.J Immunother Cancer2022;10:e004029 PMCID:PMC8919471

[72]

Pan Y,Wang X.Tumor-associated macrophages in tumor immunity.Front Immunol2020;11:583084 PMCID:PMC7751482

[73]

Deng X,Horne D,Chen J.The roles and implications of RNA m6A modification in cancer.Nat Rev Clin Oncol2023;20:507-26

[74]

Fitzsimmons CM.It’s complicated… m6A-dependent regulation of gene expression in cancer.Biochim Biophys Acta Gene Regul Mech2019;1862:382-93 PMCID:PMC6401303

[75]

Nieman KM,Penicka CV.Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth.Nat Med2011;17:1498-503 PMCID:PMC4157349

[76]

Nieman KM,Van Houten B.Adipose tissue and adipocytes support tumorigenesis and metastasis.Biochim Biophys Acta2013;1831:1533-41 PMCID:PMC3742583

[77]

Mukherjee A,Daifotis HA.Adipocyte-induced FABP4 expression in ovarian cancer cells promotes metastasis and mediates carboplatin resistance.Cancer Res2020;80:1748-61 PMCID:PMC10656748

[78]

Tan Y,Zhao G.Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells.Nat Commun2022;13:4554 PMCID:PMC9356138

[79]

Cuello MA,Liberona F.The impact on high-grade serous ovarian cancer of obesity and lipid metabolism-related gene expression patterns: the underestimated driving force affecting prognosis.J Cell Mol Med2018;22:1805-15 PMCID:PMC5824367

[80]

Guo D,Mischel P.Targeting SREBP-1-driven lipid metabolism to treat cancer.Curr Pharm Des2014;20:2619-26 PMCID:PMC4148912

[81]

Yang J.Lipid regulatory proteins as potential therapeutic targets for ovarian cancer in obese women.Cancers2020;12:3469 PMCID:PMC7700662

[82]

Li YJ,Aftabizadeh M.Fatty acid oxidation protects cancer cells from apoptosis by increasing mitochondrial membrane lipids.Cell Rep2022;39:111044

[83]

Carracedo A,Pandolfi PP.Cancer metabolism: fatty acid oxidation in the limelight.Nat Rev Cancer2013;13:227-32 PMCID:PMC3766957

[84]

Yoon H.Fatty acid metabolism in ovarian cancer: therapeutic implications.Int J Mol Sci2022;23:2170 PMCID:PMC8874779

[85]

Garcia JM,Chen JA.Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice.Endocrinology2013;154:3118-29 PMCID:PMC3749475

[86]

Cummings M,Orsi NM.Targeting the tumour microenvironment in platinum-resistant ovarian cancer.Semin Cancer Biol2021;77:3-28

[87]

Dudley AC.Tumor endothelial cells.Cold Spring Harb Perspect Med2012;2:a006536 PMCID:PMC3282494

[88]

Ghoneum A,Warren B.Exploring the clinical value of tumor microenvironment in platinum-resistant ovarian cancer.Semin Cancer Biol2021;77:83-98 PMCID:PMC8286277

[89]

Suh DH,Kim B.Metabolic orchestration between cancer cells and tumor microenvironment as a co-evolutionary source of chemoresistance in ovarian cancer: a therapeutic implication.Biochem Pharmacol2014;92:43-54

[90]

Zalcberg JR.Ripretinib for the treatment of advanced gastrointestinal stromal tumor.Therap Adv Gastroenterol2021;14:17562848211008177 PMCID:PMC8053826

[91]

Chen BJ.Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F.Leuk Lymphoma2001;42:253-65

[92]

Le F,Han Y.TPL inhibits the invasion and migration of drug-resistant ovarian cancer by targeting the PI3K/AKT/NF-κB-signaling pathway to inhibit the polarization of M2 TAMs.Front Oncol2021;11:704001 PMCID:PMC8350572

AI Summary AI Mindmap
PDF

130

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/