Identification of cancer stem cells provides novel tumor models for drug discovery

doi:10.1007/s11684-012-0199-1

Front Med

2012, Vol. 6

Issue (2) : 112-121 https://doi.org/10.1007/s11684-012-0199-1

REVIEW

Identification of cancer stem cells provides novel tumor models for drug discovery

Douglas D. Fang(

), Danyi Wen, Yajun Xu

Shanghai ChemPartner Co., Ltd., 998 Halei Road, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai 201203, China

Download: PDF(430 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

Cancer stem cells (CSCs) have received considerable attention from the research community since they were first reported in human acute myeloid leukemia 15 years ago. Accumulating evidence suggests that CSCs are responsible for tumor initiation and progression, drug resistance, and metastasis in both liquid and solid tumors. These findings lead to the development of novel compounds targeting CSC populations that is becoming increasingly important for eradicating CSCs in heterogeneous tumor masses and to cure the cancer. Since 2003, we have participated in CSC studies and encountered crucial early events in the field. This article reviews the history of CSC biology, clarifies the term and its definition, and further addresses the issue of how to utilize CSCs in therapeutic target discovery and drug development based on our substantial experience.

Keywords cancer stem cell tumor model drug discovery

Corresponding Author(s): Fang Douglas D.,Email:douglas_fang@wuxiapptec.com

Issue Date: 05 June 2012

Cite this article:

Douglas D. Fang,Danyi Wen,Yajun Xu. Identification of cancer stem cells provides novel tumor models for drug discovery[J]. Front Med, 2012, 6(2): 112-121.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0199-1
https://academic.hep.com.cn/fmd/EN/Y2012/V6/I2/112

Fig.1 Landmark publications in the earlier years of stem cell and cancer stem cell research. The indicators and mouse strains used and the principal investigators or first authors are shown for each publication. mESCs, mouse embryonic stem cells; hESCs, human embryonic stem cells; SC, stem cell; CSC, cancer stem cell.

Tab.1 Comparison of key biological properties of stem cells and CSCs

Fig.2 Identification and isolation of CSCs using cell sorting and stem cell culture technologies. Representative articles are cited.

Fig.3 CSC niche and tumor microenvironment.

Fig.4 modeling of CSC niche and tumor microenvironment by co-culturing CSCs and tumor stromal cells. A direct co-culture system may more realistically reflect a tumor microenvironment, whereas an indirect co-culture system allows for the study of not only the effects of signal proteins produced by stromal cells through a paracrine loop but also the invasive behaviors of CSCs in the presence of tumor stromal cells.

Fig.5 Use of spheroid CSC cultures for drug testing to predict antitumor activities .

Fig.6 Use of CSC-driven xenograft tumor models for efficacy studies. cultured CSCs provide a consistent cell source for the generation of xenograft tumor models. After compound treatment, xenograft tumors can be resected for analysis of CSC frequencies by flow cytometry. The self-renewal capability sustained by the remaining CSCs can be further tested by reimplantation experiments.

1	Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414(6859): 105-111 doi: 10.1038/35102167 pmid:11689955
2	Sirard C, Lapidot T, Vormoor J, Cashman JD, Doedens M, Murdoch B, Jamal N, Messner H, Addey L, Minden M, Laraya P, Keating A, Eaves A, Lansdorp PM, Eaves CJ, Dick JE. Normal and leukemic SCID-repopulating cells (SRC) coexist in the bone marrow and peripheral blood from CML patients in chronic phase, whereas leukemic SRC are detected in blast crisis. Blood 1996; 87(4): 1539-1548 pmid:8608245
3	Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282(5391): 1145-1147 doi: 10.1126/science.282.5391.1145 pmid:9804556
4	Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-3988 doi: 10.1073/pnas.0530291100 pmid:12629218
5	Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63(18): 5821-5828 pmid:14522905
6	Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature 2004; 432(7015): 396-401 doi: 10.1038/nature03128 pmid:15549107
7	Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 2005; 65(20): 9328-9337 doi: 10.1158/0008-5472.CAN-05-1343 pmid:16230395
8	Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG. Highly purified CD44⁺ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 2006; 25(12): 1696-1708 doi: 10.1038/sj.onc.1209327 pmid:16449977
9	Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007; 104(3): 973-978 doi: 10.1073/pnas.0610117104 pmid:17210912
10	Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Characterization of CD133⁺ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 2006; 351(4): 820-824 doi: 10.1016/j.bbrc.2006.10.128 pmid:17097610
11	Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM. Identification of pancreatic cancer stem cells. Cancer Res 2007; 67(3): 1030-1037 doi: 10.1158/0008-5472.CAN-06-2030 pmid:17283135
12	Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007; 1(3): 313-323 doi: 10.1016/j.stem.2007.06.002 pmid:18371365
13	O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445(7123): 106-110 doi: 10.1038/nature05372 pmid:17122772
14	Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R. Identification and expansion of human colon-cancer-initiating cells. Nature 2007; 445(7123): 111-115 doi: 10.1038/nature05384 pmid:17122771
15	Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007; 104(24): 10158-10163 doi: 10.1073/pnas.0703478104 pmid:17548814
16	Monzani E, Facchetti F, Galmozzi E, Corsini E, Benetti A, Cavazzin C, Gritti A, Piccinini A, Porro D, Santinami M, Invernici G, Parati E, Alessandri G, La Porta CA. Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer 2007; 43(5): 935-946 doi: 10.1016/j.ejca.2007.01.017 pmid:17320377
17	Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 2008; 15(3): 504-514 doi: 10.1038/sj.cdd.4402283 pmid:18049477
18	Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 2008; 68(11): 4311-4320 doi: 10.1158/0008-5472.CAN-08-0364 pmid:18519691
19	Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH. Identification of cells initiating human melanomas. Nature 2008; 451(7176): 345-349 doi: 10.1038/nature06489 pmid:18202660
20	Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST. Significance of CD90⁺ cancer stem cells in human liver cancer. Cancer Cell 2008; 13(2): 153-166 doi: 10.1016/j.ccr.2008.01.013 pmid:18242515
21	Suvà ML, Riggi N, Stehle JC, Baumer K, Tercier S, Joseph JM, Suvà D, Clément V, Provero P, Cironi L, Osterheld MC, Guillou L, Stamenkovic I. Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res 2009; 69(5): 1776-1781 doi: 10.1158/0008-5472.CAN-08-2242 pmid:19208848
22	Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fujii S, Marks JR, Berchuck A, Murphy SK. Epigenetic regulation of CD133 and tumorigenicity of CD133⁺ ovarian cancer cells. Oncogene 2009; 28(2): 209-218 doi: 10.1038/onc.2008.374 pmid:18836486
23	Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM. Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006; 66(19): 9339-9344 doi: 10.1158/0008-5472.CAN-06-3126 pmid:16990346
24	Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS. Analysis of gene expression and chemoresistance of CD133⁺ cancer stem cells in glioblastoma. Mol Cancer 2006; 5(1): 6 doi: 10.1186/1476-4598-5-6 pmid: 17140455
25	Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 2007; 1(4): 389-402 doi: 10.1016/j.stem.2007.08.001 pmid:18371377
26	Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133⁺ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008; 27(12): 1749-1758 doi: 10.1038/sj.onc.1210811 pmid:17891174
27	Phillips TM, McBride WH, Pajonk F. The response of CD24(-/low)/CD44⁺ breast cancer-initiating cells to radiation. J Natl Cancer Inst 2006; 98(24): 1777-1785 doi: 10.1093/jnci/djj495 pmid:17179479
28	Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444(7120): 756-760 doi: 10.1038/nature05236 pmid:17051156
29	Dylla SJ, Beviglia L, Park IK, Chartier C, Raval J, Ngan L, Pickell K, Aguilar J, Lazetic S, Smith-Berdan S, Clarke MF, Hoey T, Lewicki J, Gurney AL. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE 2008; 3(6): e2428 doi: 10.1371/journal.pone.0002428 pmid:18560594
30	Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133(4): 704-715 doi: 10.1016/j.cell.2008.03.027 pmid:18485877
31	Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, Houvenaeghel G, Extra JM, Bertucci F, Jacquemier J, Xerri L, Dontu G, Stassi G, Xiao Y, Barsky SH, Birnbaum D, Viens P, Wicha MS. Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res 2010; 16(1): 45-55 doi: 10.1158/1078-0432.CCR-09-1630 pmid:20028757
32	Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, Ng L, Cheung LW, Lan XR, Lan HY, Tan VP, Yau TC, Poon RT, Wong BC. A subpopulation of CD26⁺ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 2010; 6(6): 603-615 doi: 10.1016/j.stem.2010.04.001 pmid:20569697
33	Svendsen CN, ter Borg MG, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T, Caldwell MA. A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Methods 1998; 85(2): 141-152 doi: 10.1016/S0165-0270(98)00126-5 pmid:9874150
34	Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 2000; 97(26): 14720-14725 doi: 10.1073/pnas.97.26.14720 pmid:11121071
35	Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 2003; 100(25): 15178-15183 doi: 10.1073/pnas.2036535100 pmid:14645703
36	Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005; 65(13): 5506-5511 doi: 10.1158/0008-5472.CAN-05-0626 pmid:15994920
37	Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW, Ghivizzani SC, Ignatova TN, Steindler DA. Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia 2005; 7(11): 967-976 doi: 10.1593/neo.05394 pmid:16331882
38	Bapat SA, Mali AM, Koppikar CB, Kurrey NK. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 2005; 65(8): 3025-3029 pmid:15833827
39	Miki J, Furusato B, Li H, Gu Y, Takahashi H, Egawa S, Sesterhenn IA, McLeod DG, Srivastava S, Rhim JS. Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res 2007; 67(7): 3153-3161 doi: 10.1158/0008-5472.CAN-06-4429 pmid:17409422
40	Gou S, Liu T, Wang C, Yin T, Li K, Yang M, Zhou J. Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas 2007; 34(4): 429-435 doi: 10.1097/MPA.0b013e318033f9f4 pmid:17446842
41	Yu H, Fang D, Kumar SM, Li L, Nguyen TK, Acs G, Herlyn M, Xu X. Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol 2006; 168(6): 1879-1888 doi: 10.2353/ajpath.2006.051170 pmid:16723703
42	Fang DD, Kim YJ, Lee CN, Aggarwal S, McKinnon K, Mesmer D, Norton J, Birse CE, He T, Ruben SM, Moore PA. Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery. Br J Cancer 2010; 102(8): 1265-1275 doi: 10.1038/sj.bjc.6605610 pmid:20332776
43	Fang DD, Cao J, Jani J, Tsaparikos K, Blasina A, Kornmann J, Lira ME, Wang J, Bingham J, VanArsdale T, Los G, Hostomsky Z. Establishing a three-dimensional in vitro tumor spheroid model with cancer stem cell characteristics for drug evaluation (AACR annual meeting, Apr 18-22, 2009; Denver, CO)
44	Fang DD, Gu Y, Tsaparikos K, Thiel M, Jackson-Fisher A, Cao J, Zong Q, Lira ME, Jani J, Hayashi T, Schwab R, Wong A, John-Baptiste A, Lappin PB, Cheng H, Bender S, Bagrodia S, Yin MJ, VanArsdale T. Establishing patient-derived colorectal cancer stem cell models with a PIK3CA mutation for the development of inhibitory drugs as targeted therapies (AACR annual meeting, Apr 17-21, 2010; Washington DC)
45	Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W, Park JK, Fine HA. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 2006; 9(5): 391-403 doi: 10.1016/j.ccr.2006.03.030 pmid:16697959
46	De Witt Hamer PC, Van Tilborg AA, Eijk PP, Sminia P, Troost D, Van Noorden CJ, Ylstra B, Leenstra S. The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids. Oncogene 2008; 27(14): 2091-2096 doi: 10.1038/sj.onc.1210850 pmid:17934519
47	Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 2004; 101(3): 781-786 doi: 10.1073/pnas.0307618100 pmid:14711994
48	Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci USA 2010; 107(8): 3722-3727 doi: 10.1073/pnas.0915135107 pmid:20133591
49	Rappa G, Mercapide J, Anzanello F, Prasmickaite L, Xi Y, Ju J, Fodstad O, Lorico A. Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targets. Exp Cell Res 2008; 314(10): 2110-2122 doi: 10.1016/j.yexcr.2008.03.008 pmid:18423605
50	Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 2004; 101(39): 14228-14233 doi: 10.1073/pnas.0400067101 pmid:15381773
51	Fukaya R, Ohta S, Yamaguchi M, Fujii H, Kawakami Y, Kawase T, Toda M. Isolation of cancer stem-like cells from a side population of a human glioblastoma cell line, SK-MG-1. Cancer Lett 2010; 291(2): 150-157 doi: 10.1016/j.canlet.2009.10.010 pmid:19913993
52	Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, Brown M, Viens P, Xerri L, Bertucci F, Stassi G, Dontu G, Birnbaum D, Wicha MS. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res 2009; 69(4): 1302-1313 doi: 10.1158/0008-5472.CAN-08-2741 pmid:19190339
53	Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F, Korkaya H, Heath A, Dutcher J, Kleer CG, Jung Y, Dontu G, Taichman R, Wicha MS. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 2011; 71(2): 614-624 doi: 10.1158/0008-5472.CAN-10-0538 pmid:21224357
54	Goldstein RH, Reagan MR, Anderson K, Kaplan DL, Rosenblatt M. Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis. Cancer Res 2010; 70(24): 10044-10050 doi: 10.1158/0008-5472.CAN-10-1254 pmid:21159629
55	Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN, Champlin RE, Andreeff M. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004; 96(21): 1593-1603 doi: 10.1093/jnci/djh299 pmid:15523088
56	Mishra PJ, Mishra PJ, Humeniuk R, Medina DJ, Alexe G, Mesirov JP, Ganesan S, Glod JW, Banerjee D. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res 2008; 68(11): 4331-4339 doi: 10.1158/0008-5472.CAN-08-0943 pmid:18519693
57	Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, Andreeff M, Marini F. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS ONE 2009; 4(4): e4992 doi: 10.1371/journal.pone.0004992 pmid:19352430
58	Bagley RG, Weber W, Rouleau C, Yao M, Honma N, Kataoka S, Ishida I, Roberts BL, Teicher BA. Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers. Int J Oncol 2009; 34(3): 619-627 doi: 10.3892/ijo_00000187 pmid:19212666
59	Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007; 449(7162): 557-563 doi: 10.1038/nature06188 pmid:17914389
60	Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, Tanaka S, Yasui W, Chayama K. Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer 2010; 127(10): 2323-2333 doi: 10.1002/ijc.25440 pmid:20473928
61	Lis R, Touboul C, Mirshahi P, Ali F, Mathew S, Nolan DJ, Maleki M, Abdalla SA, Raynaud CM, Querleu D, Al-Azwani E, Malek J, Mirshahi M, Rafii A. Tumor associated mesenchymal stem cells protects ovarian cancer cells from hyperthermia through CXCL12. Int J Cancer 2011; 128(3): 715-725 doi: 10.1002/ijc.25619 pmid:20725999
62	McMillin DW, Delmore J, Weisberg E, Negri JM, Geer DC, Klippel S, Mitsiades N, Schlossman RL, Munshi NC, Kung AL, Griffin JD, Richardson PG, Anderson KC, Mitsiades CS. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med 2010; 16(4): 483-489 doi: 10.1038/nm.2112 pmid:20228816
63	Lee J, Fassnacht M, Nair S, Boczkowski D, Gilboa E. Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts. Cancer Res 2005; 65(23): 11156-11163 doi: 10.1158/0008-5472.CAN-05-2805 pmid:16322266
64	Schwartz DL, Powis G, Thitai-Kumar A, He Y, Bankson J, Williams R, Lemos R, Oh J, Volgin A, Soghomonyan S, Nishii R, Alauddin M, Mukhopadhay U, Peng Z, Bornmann W, Gelovani J. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol Cancer Ther 2009; 8(4): 947-958 doi: 10.1158/1535-7163.MCT-08-0981 pmid:19372568
65	Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, Denicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, Reichelt S, Howat WJ, Chang A, Dhara M, Wang L, Rückert F, Grützmann R, Pilarsky C, Izeradjene K, Hingorani SR, Huang P, Davies SE, Plunkett W, Egorin M, Hruban RH, Whitebread N, McGovern K, Adams J, Iacobuzio-Donahue C, Griffiths J, Tuveson DA. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009; 324(5933): 1457-1461 doi: 10.1126/science.1171362 pmid:19460966
66	Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 2009; 457(7229): 603-607 doi: 10.1038/nature07589 pmid:19092805
67	Liu HK, Wang Y, Belz T, Bock D, Takacs A, Radlwimmer B, Barbus S, Reifenberger G, Lichter P, Schütz G. The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation. Genes Dev 2010; 24(7): 683-695 doi: 10.1101/gad.560310 pmid:20360385
68	Youssef KK, Van Keymeulen A, Lapouge G, Beck B, Michaux C, Achouri Y, Sotiropoulou PA, Blanpain C. Identification of the cell lineage at the origin of basal cell carcinoma. Nat Cell Biol 2010; 12(3): 299-305 pmid:20154679
69	Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, kConFab, Fox SB, Yan M, French JD, Brown MA, Smyth GK, Visvader JE, Lindeman GJ. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 2009; 15(8): 907-913 doi: 10.1038/nm.2000 pmid:19648928
70	Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, Tamaki Y, Noguchi S. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res 2009; 15(12): 4234-4241 doi: 10.1158/1078-0432.CCR-08-1479 pmid:19509181

[1]

Yun Zhang, Robert A. Weinberg. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities[J]. Front. Med., 2018, 12(4): 361-373.

[2]

Douglas D. Fang, Joan Cao, Jitesh P. Jani, Konstantinos Tsaparikos, Alessandra Blasina, Jill Kornmann, Maruja E. Lira, Jianying Wang, Zuzana Jirout, Justin Bingham, Zhou Zhu, Yin Gu, Gerrit Los, Zdenek Hostomsky, Todd VanArsdale. Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-like cells enriched with tumor spheroids from a non-small cell lung cancer cell line[J]. Front Med, 2013, 7(4): 462-476.

Viewed

Full text

Abstract

Cited

Shared

Discussed