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Published in: Cancer Cell International 1/2013

Open Access 01-12-2013 | Primary research

Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice

Authors: Wenxing Yan, Yubing Chen, Yueliang Yao, Hongmei Zhang, Tiejun Wang

Published in: Cancer Cell International | Issue 1/2013

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Abstract

Background

Identification of cancer stem cells (CSCs) and their behaviors will provide insightful information for the future control of human cancers. This study investigated CD44 and CD24 cell surface markers as breast cancer CSC markers in vitro and in vivo.

Methods

Flow cytometry with CD44 and CD24 markers was used to sort breast cancer MCF7 cells for scanning electron microscopy (SEM), tumor cell invasion assay, and nude mouse xenograft assay.

Results

Flow cytometry assay using CD44 and CD24 markers sorted MCF7 cells into four subsets, i.e., CD44+/CD24-/low, CD44-/CD24+, CD44+/CD24+, and CD44-/CD24-. The SEM data showed that there were many protrusions on the surface of CD44+/CD24-/low cells. CD44+/CD24-/low cells had many microvilli and pseudopodia. The CD44+/CD24-/low cells had a higher migration and invasion abilities than that of the other three subsets of the cells. The in vivo tumor formation assay revealed that CD44+/CD24- cells had the highest tumorigenic capacity compared to the other three subsets.

Conclusion

CD44 and CD24 could be useful markers for identification of breast CSCs because CD44+/CD24-/low cells had unique surface ultrastructures and the highest tumorigenicity and invasive abilities.
Appendix
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Literature
1.
go back to reference Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF: Therapeutic implications of cancer stem cells. Curr Opin Genet Dev. 2004, 14: 43-47. 10.1016/j.gde.2003.11.007.CrossRefPubMed Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF: Therapeutic implications of cancer stem cells. Curr Opin Genet Dev. 2004, 14: 43-47. 10.1016/j.gde.2003.11.007.CrossRefPubMed
2.
go back to reference 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: 3983-3988. 10.1073/pnas.0530291100.PubMedCentralCrossRefPubMed 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: 3983-3988. 10.1073/pnas.0530291100.PubMedCentralCrossRefPubMed
3.
go back to reference 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: 1302-1313. 10.1158/0008-5472.CAN-08-2741.PubMedCentralCrossRefPubMed 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: 1302-1313. 10.1158/0008-5472.CAN-08-2741.PubMedCentralCrossRefPubMed
4.
go back to reference Li F, Tiede B, Kang Y, Massagué J: Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res. 2007, 17: 3-14. 10.1038/sj.cr.7310118.CrossRefPubMed Li F, Tiede B, Kang Y, Massagué J: Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res. 2007, 17: 3-14. 10.1038/sj.cr.7310118.CrossRefPubMed
5.
go back to reference Velasco-Velázquez MA, Popov VM, Lisanti MP, Pestell RG: The role of breast cancer stem cells in metastasis and therapeutic implications. Am J Pathol. 2011, 179: 2-11. 10.1016/j.ajpath.2011.03.005.PubMedCentralCrossRefPubMed Velasco-Velázquez MA, Popov VM, Lisanti MP, Pestell RG: The role of breast cancer stem cells in metastasis and therapeutic implications. Am J Pathol. 2011, 179: 2-11. 10.1016/j.ajpath.2011.03.005.PubMedCentralCrossRefPubMed
6.
go back to reference Dean M, Fojo T, Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 2005, 5: 275-284. 10.1038/nrc1590.CrossRefPubMed Dean M, Fojo T, Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 2005, 5: 275-284. 10.1038/nrc1590.CrossRefPubMed
7.
go back to reference 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: 5821-5828.PubMed 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: 5821-5828.PubMed
8.
go back to reference 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: 106-110. 10.1038/nature05372.CrossRefPubMed 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: 106-110. 10.1038/nature05372.CrossRefPubMed
9.
go back to reference 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: 4311-4320. 10.1158/0008-5472.CAN-08-0364.PubMedCentralCrossRefPubMed 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: 4311-4320. 10.1158/0008-5472.CAN-08-0364.PubMedCentralCrossRefPubMed
10.
go back to reference Tsuchiya S, Li F: Electron microscopic findings for diagnosis of breast lesions. Med Mol Morphol. 2005, 38: 216-224. 10.1007/s00795-005-0300-9.CrossRefPubMed Tsuchiya S, Li F: Electron microscopic findings for diagnosis of breast lesions. Med Mol Morphol. 2005, 38: 216-224. 10.1007/s00795-005-0300-9.CrossRefPubMed
11.
go back to reference Zhao YD, Huang Q, Zhang TY, Dong J, Wang AD, Ding F, Lan Q, Gu XS, Qin ZH: [Ultrastructural analysis of glioma stem cells-progenitors]. Zhonghua Zhong Liu Za Zhi. 2008, 30: 663-667.PubMed Zhao YD, Huang Q, Zhang TY, Dong J, Wang AD, Ding F, Lan Q, Gu XS, Qin ZH: [Ultrastructural analysis of glioma stem cells-progenitors]. Zhonghua Zhong Liu Za Zhi. 2008, 30: 663-667.PubMed
12.
go back to reference Paniz Mondolfi AE, Slova D, Fan W, Attiyeh FF, Afthinos J, Reidy J, Pang Y, Theise ND: Mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: a possible stem cell tumor?. Pathol Int. 2011, 61: 608-614. 10.1111/j.1440-1827.2011.02709.x.CrossRefPubMed Paniz Mondolfi AE, Slova D, Fan W, Attiyeh FF, Afthinos J, Reidy J, Pang Y, Theise ND: Mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: a possible stem cell tumor?. Pathol Int. 2011, 61: 608-614. 10.1111/j.1440-1827.2011.02709.x.CrossRefPubMed
13.
go back to reference Pham PV, Phan NL, Nguyen NT, Truong NH, Duong TT, Le DV, Truong KD, Phan NK: Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy. J Transl Med. 2011, 9: 209-10.1186/1479-5876-9-209.PubMedCentralCrossRefPubMed Pham PV, Phan NL, Nguyen NT, Truong NH, Duong TT, Le DV, Truong KD, Phan NK: Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy. J Transl Med. 2011, 9: 209-10.1186/1479-5876-9-209.PubMedCentralCrossRefPubMed
15.
go back to reference Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K: Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007, 11: 259-273. 10.1016/j.ccr.2007.01.013.CrossRefPubMed Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K: Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007, 11: 259-273. 10.1016/j.ccr.2007.01.013.CrossRefPubMed
16.
go back to reference Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H: Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005, 11: 1154-1159.PubMed Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H: Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005, 11: 1154-1159.PubMed
18.
go back to reference Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K: Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 2010, 16: 876-887. 10.1158/1078-0432.CCR-09-1532.PubMedCentralCrossRefPubMed Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K: Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 2010, 16: 876-887. 10.1158/1078-0432.CCR-09-1532.PubMedCentralCrossRefPubMed
19.
go back to reference Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007, 1: 555-567. 10.1016/j.stem.2007.08.014.PubMedCentralCrossRefPubMed Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007, 1: 555-567. 10.1016/j.stem.2007.08.014.PubMedCentralCrossRefPubMed
20.
go back to reference Smith GH, Chepko G: Mammary epithelial stem cells. Microsc Res Tech. 2001, 52: 190-203. 10.1002/1097-0029(20010115)52:2<190::AID-JEMT1005>3.0.CO;2-O.CrossRefPubMed Smith GH, Chepko G: Mammary epithelial stem cells. Microsc Res Tech. 2001, 52: 190-203. 10.1002/1097-0029(20010115)52:2<190::AID-JEMT1005>3.0.CO;2-O.CrossRefPubMed
21.
go back to reference Chepko G, Dickson RB: Ultrastructure of the putative stem cell niche in rat mammary epithelium. Tissue Cell. 2003, 35: 83-93. 10.1016/S0040-8166(02)00107-6.CrossRefPubMed Chepko G, Dickson RB: Ultrastructure of the putative stem cell niche in rat mammary epithelium. Tissue Cell. 2003, 35: 83-93. 10.1016/S0040-8166(02)00107-6.CrossRefPubMed
22.
go back to reference Pierce GB, Nakane PK, Martinez-Hernandez A, Ward JM: Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts. J Natl Cancer Inst. 1977, 58: 1329-1345.PubMed Pierce GB, Nakane PK, Martinez-Hernandez A, Ward JM: Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts. J Natl Cancer Inst. 1977, 58: 1329-1345.PubMed
23.
go back to reference Black PH: Shedding from the cell surface of normal and cancer cells. Adv Cancer Res. 1980, 32: 75-199.CrossRefPubMed Black PH: Shedding from the cell surface of normal and cancer cells. Adv Cancer Res. 1980, 32: 75-199.CrossRefPubMed
24.
go back to reference Nicolson GL, Poste G: The cancer cell: dynamic aspects and modifications in cell-surface organization (first of two parts). N Engl J Med. 1976, 295: 197-203. 10.1056/NEJM197607222950405.CrossRefPubMed Nicolson GL, Poste G: The cancer cell: dynamic aspects and modifications in cell-surface organization (first of two parts). N Engl J Med. 1976, 295: 197-203. 10.1056/NEJM197607222950405.CrossRefPubMed
25.
go back to reference Spring FA, Dalchau R, Daniels GL, Mallinson G, Judson PA, Parsons SF, Fabre JW, Anstee DJ: The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene. Immunology. 1988, 64: 37-43.PubMedCentralPubMed Spring FA, Dalchau R, Daniels GL, Mallinson G, Judson PA, Parsons SF, Fabre JW, Anstee DJ: The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene. Immunology. 1988, 64: 37-43.PubMedCentralPubMed
26.
go back to reference Sillanpää S, Anttila MA, Voutilainen K, Tammi RH, Tammi MI, Saarikoski SV, Kosma VM: CD44 expression indicates favorable prognosis in epithelial ovarian cancer. Clin Cancer Res. 2003, 9: 5318-5324.PubMed Sillanpää S, Anttila MA, Voutilainen K, Tammi RH, Tammi MI, Saarikoski SV, Kosma VM: CD44 expression indicates favorable prognosis in epithelial ovarian cancer. Clin Cancer Res. 2003, 9: 5318-5324.PubMed
27.
go back to reference Li D, Zheng L, Jin L, Zhou Y, Li H, Fu J, Shi M, Du P, Wang L, Wu H, Chen GY, Zheng P, Liu Y, Wang FS, Wang S: CD24 polymorphisms affect risk and progression of chronic hepatitis B virus infection. Hepatology. 2009, 50: 735-742. 10.1002/hep.23047.CrossRefPubMed Li D, Zheng L, Jin L, Zhou Y, Li H, Fu J, Shi M, Du P, Wang L, Wu H, Chen GY, Zheng P, Liu Y, Wang FS, Wang S: CD24 polymorphisms affect risk and progression of chronic hepatitis B virus infection. Hepatology. 2009, 50: 735-742. 10.1002/hep.23047.CrossRefPubMed
28.
go back to reference Nestl A, Von Stein OD, Zatloukal K, Thies WG, Herrlich P, Hofmann M, Sleeman JP: Gene expression patterns associated with the metastatic phenotype in rodent and human tumors. Cancer Res. 2001, 61: 1569-1577.PubMed Nestl A, Von Stein OD, Zatloukal K, Thies WG, Herrlich P, Hofmann M, Sleeman JP: Gene expression patterns associated with the metastatic phenotype in rodent and human tumors. Cancer Res. 2001, 61: 1569-1577.PubMed
29.
go back to reference Aigner S, Ruppert M, Hubbe M, Sammar M, Sthoeger Z, Butcher EC, Vestweber D, Altevogt P: Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. Int Immunol. 1995, 7: 1557-1565. 10.1093/intimm/7.10.1557.CrossRefPubMed Aigner S, Ruppert M, Hubbe M, Sammar M, Sthoeger Z, Butcher EC, Vestweber D, Altevogt P: Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. Int Immunol. 1995, 7: 1557-1565. 10.1093/intimm/7.10.1557.CrossRefPubMed
30.
go back to reference Magee JA, Piskounova E, Morrison SJ: Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012, 21: 283-296. 10.1016/j.ccr.2012.03.003.PubMedCentralCrossRefPubMed Magee JA, Piskounova E, Morrison SJ: Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012, 21: 283-296. 10.1016/j.ccr.2012.03.003.PubMedCentralCrossRefPubMed
Metadata
Title
Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice
Authors
Wenxing Yan
Yubing Chen
Yueliang Yao
Hongmei Zhang
Tiejun Wang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2013
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-13-62

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