Therapeutic targets against gastric cancer stem cells interacting with tumor microenvironment

Abstract

Gastric cancer (GC) is a major cause of cancer-related deaths worldwide. The existence of cancer stem cells (CSCs) is known to be the main reason for resistance to anticancer agents as well as for the development of distant metastases. Although CSCs themselves harbor self-renewal and differentiation abilities, the tumor microenvironment that surrounds CSCs provides secreted factors and supports angiogenesis and is thus responsible for the maintenance of their CSC properties. The current review provides information regarding the impact of the tumor microenvironment on gastric CSCs, which will support the development of novel therapeutic strategies for targeting gastric CSCs.

Keywords

Gastric cancer stem cells / stem cell markers / tumor microenvironment / gastric cancer treatment

References

[1] Bertuccio P,Levi F,Ferlay J,Malvezzi M.Recent patterns in gastric cancer: a global overview..Int J Cancer2009;125:666-73

[2] Taghavi S,Davey A.Prognostic significance of signet ring gastric cancer..J Clin Oncol2012;30:3493-8 PMCID:PMC3454770

[3] Jemal A,Center MM,Ward E.Global cancer statistics..CA Cancer J Clin2011;61:69-90

[4] Hohenberger P.Gastric cancer..Lancet2003;362:305-15

[5] Clarke MF.Stem cells and cancer: two faces of eve..Cell2006;124:1111-5

[6] Visvader JE.Cancer stem cells: current status and evolving complexities..Cell Stem Cell2012;10:717-28

[7] Jordan CT,Noble M.Cancer stem cells..N Engl J Med2006;355:1253-61

[8] Furth J,Breedis C.The transmission of leukemia of mice with a single cell..Am J Cancer1937;31:276-82

[9] Bonnet D.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell..Nat Med1997;3:730-7

[10] Ricci-Vitiani L,Pilozzi E,Todaro M,De Maria R.Identification and expansion of human colon-cancer-initiating cells..Nature2007;445:111-5

[11] Singh SK,Terasaki M,Hawkins C,Dirks PB.Identification of a cancer stem cell in human brain tumors..Cancer Res2003;63:5821-8

[12] Al-Hajj M,Benito-Hernandez A,Clarke MF.Prospective identification of tumorigenic breast cancer cells..Proc Natl Acad Sci U S A2003;100:3983-8 PMCID:PMC153034

[13] Xu G,Ou Yang X,Su X.Cancer stem cells: the "heartbeat" of gastric cancer..J Gastroenterol2013;48:781-97

[14] Singh SR.Gastric cancer stem cells: a novel therapeutic target..Cancer Lett2013;338:110-9 PMCID:PMC3755024

[15] Vermeulen L,de Sousa Mello F,Kemper K,Richel DJ,Medema JP.Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity..Proc Natl Acad Sci U S A2008;105:13427-32 PMCID:PMC2533206

[16] Takaishi S,Tu S,Shibata W,Gordon SA,Wang TC.Identification of gastric cancer stem cells using the cell surface marker CD44..Stem Cells2009;27:1006-20 PMCID:PMC2746367

[17] Zhang C,He F,Yang H.Identification of CD44+CD24+ gastric cancer stem cells..J Cancer Res Clin Oncol2011;137:1679-86

[18] Chen T,Yu J,Yuan D,Liu F,Dai B,Wang F,Xu H,Mo X.Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients..Cell Res2012;22:248-58 PMCID:PMC3351913

[19] Han ME,Hwang SH,Kim HJ,Yoon S,Kim BS,Oh SO.Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research..Cell Mol Life Sci2011;68:3589-605

[20] Barker N,Kuipers J,van den Born M,Haegebarth A,Begthel H,Clevers H.Identification of stem cells in small intestine and colon by marker gene Lgr5..Nature2007;449:1003-7

[21] Barker N,Kujala P,Snippert HJ,Sato T,Begthel H,Danenberg E,Korving J,Peters PJ,Poulsom R.Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro..Cell Stem Cell2010;6:25-36

[22] Sato T,Snippert HJ,Vries RG,Barker N,van de Wetering M.Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts..Nature2011;469:415-8 PMCID:PMC3547360

[23] Demitrack ES,Keeley TM,VanDussen KL,Giordano TJ,Kopan R.Notch signaling regulates gastric antral LGR5 stem cell function..EMBO J2015;34:2522-36 PMCID:PMC4609184

[24] Leushacke M,Wong A,Hajamohideen A,Goh J,Denil SLIJ,Barker N.Lgr5-expressing chief cells drive epithelial regeneration and cancer in the oxyntic stomach..Nat Cell Biol2017;19:774-86

[25] Jiang Y,Li H,Zhang L,Sun YM,Jin XM.Expressions of putative cancer stem cell markers ABCB1, ABCG2, and CD133 are correlated with the degree of differentiation of gastric cancer..Gastric Cancer2012;15:440-50

[26] Hashimoto K,Isobe T,Shirouzu K.Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer..Gastric Cancer2014;17:97-106 PMCID:PMC3889295

[27] Katsuno Y,Yashiro M,Hirakawa K.Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-beta..J Pathol2012;228:391-404

[28] Nguyen PH,Chambonnier L,Wittkop L,Collet D,Evrard S,Senant-Dugot N,Mazurier F.Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma..Clin Cancer Res2017;23:1586-97

[29] Bang YJ,Feyereislova A,Shen L,Lordick F,Omuro Y,Aprile G,Hill J,Rüschoff J.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial..Lancet2010;376:687-97

[30] Jiang J,Chuai S,Zheng D,Zhang Y,Liang Y.Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype..Oncogene2012;31:671-82

[31] Ohkuma M,Ishii H,Tanaka F,Shimomura M,Yanaga K.Absence of CD71 transferrin receptor characterizes human gastric adenosquamous carcinoma stem cells..Ann Surg Oncol2012;19:1357-64

[32] Choi E,Vlacich G,Samuelson LC,Goldenring JR.Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach..Gut2017;

[33] Hayakawa Y,Stancikova J,Asfaha S,Dubeykovskaya ZA,Wang H,Chen X,Kim W,Tailor Y,Tomita H,Sepulveda AR,Gershon MD,Ding L,Fox JG,Konieczny SF,Korinek V.Mist1 expressing gastric stem cells maintain the normal and neoplastic gastric epithelium and are supported by a perivascular stem cell niche..Cancer Cell2015;28:800-14 PMCID:PMC4684751

[34] Quail DF.Microenvironmental regulation of tumor progression and metastasis..Nat Med2013;19:1423-37 PMCID:PMC3954707

[35] Ishimoto T,Nandi T,Onishi N,Lin SJ,Tay ST,Cho BC,Arima K,Iwatsuki M,Oki E,Saya H,Baba H.Activation of transforming growth factor beta 1 signaling in gastric cancer-associated fibroblasts increases their motility, via expression of rhomboid 5 homolog 2, and ability to induce invasiveness of gastric cancer cells..Gastroenterology2017;153:191-204.e16

[36] Leedham SJ,Preston SL,Wright NA.The stomach periglandular fibroblast sheath: all present and correct..Gut2006;55:295-6 PMCID:PMC1856511

[37] Hoffmann W.Stem cells, self-renewal and cancer of the gastric epithelium..Curr Med Chem2012;19:5975-83

[38] Nabet BY,Shabason JE,Yoon T,Benci JL,Tchou J,Minn AJ.Exosome RNA unshielding couples stromal activation to pattern recognition receptor signaling in cancer..Cell2017;170:352-66.e13

[39] Schofield R.The relationship between the spleen colony-forming cell and the haemopoietic stem cell..Blood Cells1978;4:7-25

[40] Moore KA.Stem cells and their niches..Science2006;311:1880-5

[41] Boral D.Cancer stem cells and niche mircoenvironments..Front Biosci (Elite Ed)2012;4:2502-14

[42] Yi SY,Nan KJ.Cancer stem cells niche: a target for novel cancer therapeutics..Cancer Treat Rev2013;39:290-6

[43] Kalluri R.The biology and function of fibroblasts in cancer..Nat Rev Cancer2016;16:582-98

[44] Hasegawa T,Nishii T,Fuyuhiro Y,Fukuoka T,Shimizu T,Hirakawa K.Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-beta signaling..Int J Cancer2014;134:1785-95

[45] Bie Q,Sun C,Barnie PA,Peng J,Zheng D,Wang S.IL-17B activated mesenchymal stem cells enhance proliferation and migration of gastric cancer cells..Oncotarget2017;8:18914-23 PMCID:PMC5386657

[46] Hayakawa Y,Konishi M,Niikura R,Renz BW,Macchini M,Jiang Z,Dubeykovskaya ZA,Chen X,Nagar K,Quante M,Gershon MD,Zhao CM,Worthley DL,Wang TC.Nerve growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling..Cancer Cell2017;31:21-34 PMCID:PMC5225031

[47] Sawaki A,Omuro Y,Hamamoto Y,Miyata Y,Yamaguchi K,Nishina T,Baba E,Abe T,Ohtsu A.Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study..Gastric Cancer2012;15:313-22in Japanese PMCID:PMC3390686

[48] Yamaguchi K,Doi T,Yamada Y,Nishina T,Chin K,Takiuchi H,Saji S,Miyata Y,Baba E,Abe T.Efficacy and safety of capecitabine plus cisplatin in Japanese patients with advanced or metastatic gastric cancer: subset analyses of the AVAGAST study and the ToGA study..Gastric Cancer2013;16:175-82in Japanese PMCID:PMC3627028

[49] Wilke H,Van Cutsem E,Bodoky G,Hironaka S,Lipatov O,Cunningham D,Komatsu Y,Emig M,Ferry D,Schwartz JD.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial..Lancet Oncol2014;15:1224-35

[50] Shitara K,Shimada Y,Sugimoto N,Nishina T,Segawa Y,Tamura T,Yukisawa S,Nagashima F,Esaki T,Chandrawansa K,Wilke H,Ohtsu A.Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer..Gastric Cancer2016;19:927-38in Japanese

[51] Topalian SL,Pardoll DM.Immune checkpoint blockade: a common denominator approach to cancer therapy..Cancer Cell2015;27:450-61 PMCID:PMC4400238

[52] Kang YK,Ryu MH,Kato K,Chen JS,Kang WK,Oh SC,Lee KW,Chen LT.Nivolumab (ONO-4538/BMS-936558) as salvage treatment after second or later-line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): a double-blinded, randomized, phase III trial..J Clin Oncol2017;35:2

[53] Ishimoto T,Yae T,Motohara T,Oshima M,Asaba R,Masuko T,Ishikawa T,Takahashi E,Baba Y,Suematsu M,Saya H.CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth..Cancer Cell2011;19:387-400

[54] Nagano O,Saya H.Redox regulation in stem-like cancer cells by CD44 variant isoforms..Oncogene2013;32:5191-8

[55] Wada T,Seishima R,Yoshikawa M,Oshima M,Wright NA,Hirashima K,Kitagawa Y,Nagano O.Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia..Cancer Sci2013;104:1323-9

[56] Smith LM,Ryan MC,Jonas M,Zabinski RF,Gerber HP,Moore PA,Carter PJ.CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers..Br J Cancer2008;99:100-9

[57] Roesch A,Schmidt EC,Brafford PA,Basu D,Vogt T.A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth..Cell2010;141:583-94

[58] Xu YY,Yang LQ,Yu C,Pang TH,Zou XP,Wang L,Huang Q.Regulation of CD44v6 expression in gastric carcinoma by the IL-6/STAT3 signaling pathway and its clinical significance..Oncotarget2017;8:45848-61

[59] Phesse TJ.Lgr5 joins the club of gastric stem cell markers in the corpus..Nat Cell Biol2017;19:752-4

[60] Li XB,Zhu L,Zhang C,Yang X.Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice..Cell Res2016;26:838-49 PMCID:PMC5129876

[61] Gong X,Ghosh SC,An Z,Carmon KS.LGR5-targeted antibody-drug conjugate eradicates gastrointestinal tumors and prevents recurrence..Mol Cancer Ther2016;15:1580-90

[62] Zhang L,Zhang D,Qin L,Zhang L.Upregulated miR-132 in Lgr5(+) gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway..Mol Carcinog2017;56:2022-34

[63] Wen L,Yang K,Zhang B,Zhou ZG,Hu JK.Prognostic value of cancer stem cell marker CD133 expression in gastric cancer: a systematic review..PLoS One2013;8:e59154 PMCID:PMC3606413