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Breast Cancer Research
Published in: Breast Cancer Research 5/2006

Open Access 01-10-2006 | Research article

CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis

Authors: Carol Sheridan, Hiromitsu Kishimoto, Robyn K Fuchs, Sanjana Mehrotra, Poornima Bhat-Nakshatri, Charles H Turner, Robert Goulet Jr, Sunil Badve, Harikrishna Nakshatri

Published in: Breast Cancer Research | Issue 5/2006

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Abstract

Introduction

A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis.

Methods

CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively.

Results

Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44+/CD24- cells. Cell lines with high CD44+/CD24- cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44+/CD24- population than in other cell lines. Among the CD44+/CD24--positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44+/CD24- subpopulation were more invasive than other cell lines. However, only a subset of CD44+/CD24--positive cell lines was able to home and proliferate in lungs.

Conclusion

Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis.
Appendix
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Literature
1.
Smalley M, Ashworth A: Stem cells and breast cancer: a field in transit. Nat Rev Cancer. 2003, 3: 832-844. 10.1038/nrc1212.CrossRefPubMed
2.
Dontu G, El-Ashry D, Wicha MS: Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol Metab. 2004, 15: 193-197. 10.1016/j.tem.2004.05.011.CrossRefPubMed
3.
Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414: 105-111. 10.1038/35102167.CrossRefPubMed
4.
Behbod F, Rosen JM: Will cancer stem cells provide new therapeutic targets?. Carcinogenesis. 2005, 26: 703-711. 10.1093/carcin/bgh293.CrossRefPubMed
5.
Dean M, Fojo T, Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 2005, 5: 275-284. 10.1038/nrc1590.CrossRefPubMed
6.
Jordan CT, Guzman ML: Mechanisms controlling pathogenesis and survival of leukemic stem cells. Oncogene. 2004, 23: 7178-7187. 10.1038/sj.onc.1207935.CrossRefPubMed
7.
Singh SK, Clarke ID, Hide T, Dirks PB: Cancer stem cells in nervous system tumors. Oncogene. 2004, 23: 7267-7273. 10.1038/sj.onc.1207946.CrossRefPubMed
8.
Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M: Stem cells and cancer; the polycomb connection. Cell. 2004, 118: 409-418. 10.1016/j.cell.2004.08.005.CrossRefPubMed
9.
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.CrossRefPubMedPubMedCentral
10.
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: 5506-5511. 10.1158/0008-5472.CAN-05-0626.CrossRefPubMed
11.
Chambers AF, Matrisian LM: Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997, 89: 1260-1270. 10.1093/jnci/89.17.1260.CrossRefPubMed
12.
Edwards DR, Murphy G: Cancer. Proteases: invasion and more [news]. Nature. 1998, 394: 527-528. 10.1038/28961.CrossRefPubMed
13.
Dumont N, Arteaga CL: Targeting the TGF beta signaling network in human neoplasia. Cancer Cell. 2003, 3: 531-536. 10.1016/S1535-6108(03)00135-1.CrossRefPubMed
14.
Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J: A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003, 3: 537-549. 10.1016/S1535-6108(03)00132-6.CrossRefPubMed
15.
Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M, Ponomarev V, Gerald WL, Blasberg R, Massague J: Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest. 2005, 115: 44-55. 10.1172/JCI200522320.CrossRefPubMedPubMedCentral
16.
Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, Morony S, Rubin E, Sarao R, Hojilla CV, et al: Regulation of cancer cell migration and bone metastasis by RANKL. Nature. 2006, 440: 692-696. 10.1038/nature04524.CrossRefPubMed
17.
18.
van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002, 415: 530-536. 10.1038/415530a.CrossRefPubMed
19.
Pantel K, Brakenhoff RH: Dissecting the metastatic cascade. Nat Rev Cancer. 2004, 4: 448-456. 10.1038/nrc1370.CrossRefPubMed
20.
Bhat-Nakshatri P, Newton TR, Goulet R, Nakshatri H: NF-kappaB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1alpha. Proc Natl Acad Sci USA. 1998, 95: 6971-6976. 10.1073/pnas.95.12.6971.CrossRefPubMedPubMedCentral
21.
Bendre MS, Gaddy-Kurten D, Mon-Foote T, Akel NS, Skinner RA, Nicholas RW, Suva LJ: Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo. Cancer Res. 2002, 62: 5571-5579.PubMed
22.
23.
Helbig G, Christopherson KW, Bhat-Nakshatri P, Kumar S, Kishimoto H, Miller KD, Broxmeyer HE, Nakshatri H: NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem. 2003, 278: 21631-21638. 10.1074/jbc.M300609200.CrossRefPubMed
24.
Thompson EW, Paik S, Brunner N, Sommers CL, Zugmaier G, Clarke R, Shima TB, Torri J, Donahue S, Lippman ME, et al: Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J Cell Physiol. 1992, 150: 534-544. 10.1002/jcp.1041500314.CrossRefPubMed
25.
Charafe-Jauffret E, Ginestier C, Monville F, Finetti P, Adelaide J, Cervera N, Fekairi S, Xerri L, Jacquemier J, Birnbaum D, et al: Gene expression profiling of breast cell lines identifies potential new basal markers. Oncogene. 2006, 25: 2273-2284. 10.1038/sj.onc.1209254.CrossRefPubMed
26.
Elstrodt F, Hollestelle A, Nagel JH, Gorin M, Wasielewski M, van den Ouweland A, Merajver SD, Ethier SP, Schutte M: BRCA1 mutation analysis of 41 human breast cancer cell lines reveals three new deleterious mutants. Cancer Res. 2006, 66: 41-45. 10.1158/0008-5472.CAN-05-2853.CrossRefPubMed
27.
Gordon LA, Mulligan KT, Maxwell-Jones H, Adams M, Walker RA, Jones JL: Breast cell invasive potential relates to the myoepithelial phenotype. Int J Cancer. 2003, 106: 8-16. 10.1002/ijc.11172.CrossRefPubMed
28.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98: 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral
29.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed
30.
Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J: Genes that mediate breast cancer metastasis to lung. Nature. 2005, 436: 518-524. 10.1038/nature03799.CrossRefPubMedPubMedCentral
31.
Mundy GR: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002, 2: 584-593. 10.1038/nrc867.CrossRefPubMed
32.
Yi B, Williams PJ, Niewolna M, Wang Y, Yoneda T: Tumor-derived platelet-derived growth factor-BB plays a critical role in osteosclerotic bone metastasis in an animal model of human breast cancer. Cancer Res. 2002, 62: 917-923.PubMed
33.
Hoffman RM: Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Invest New Drugs. 1999, 17: 343-359. 10.1023/A:1006326203858.CrossRefPubMed
34.
Edwards PA: Metastasis: the role of chance in malignancy. Nature. 2002, 419: 559-560. 10.1038/419559b.CrossRefPubMed
35.
Bourguignon LY: CD44-mediated oncogenic signaling and cytoskeleton activation during mammary tumor progression. J Mammary Gland Biol Neoplasia. 2001, 6: 287-297. 10.1023/A:1011371523994.CrossRefPubMed
36.
Hill A, McFarlane S, Mulligan K, Gillespie H, Draffin JE, Trimble A, Ouhtit A, Johnston PG, Harkin DP, McCormick D, et al: Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells. Oncogene. 2006, 25: 6079-6091. 10.1038/sj.onc.1209628.CrossRefPubMed
37.
Lopez JI, Camenisch TD, Stevens MV, Sands BJ, McDonald J, Schroeder JA: CD44 attenuates metastatic invasion during breast cancer progression. Cancer Res. 2005, 65: 6755-6763. 10.1158/0008-5472.CAN-05-0863.CrossRefPubMed
38.
Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP: CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res. 2005, 65: 10783-10793. 10.1158/0008-5472.CAN-05-0619.CrossRefPubMed
39.
Schabath H, Runz S, Joumaa S, Altevogt P: CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells. J Cell Sci. 2006, 119: 314-325. 10.1242/jcs.02741.CrossRefPubMed
40.
Gilles C, Polette M, Zahm JM, Tournier JM, Volders L, Foidart JM, Birembaut P: Vimentin contributes to human mammary epithelial cell migration. J Cell Sci. 1999, 112: 4615-4625.PubMed
41.
Gilles C, Bassuk JA, Pulyaeva H, Sage EH, Foidart JM, Thompson EW: SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res. 1998, 58: 5529-5536.PubMed
42.
Price JE: Metastasis from human breast cancer cell lines. Breast Cancer Res Treat. 1996, 39: 93-102. 10.1007/BF01806081.CrossRefPubMed
43.
Kuperwasser C, Dessain S, Bierbaum BE, Garnet D, Sperandio K, Gauvin GP, Naber SP, Weinberg RA, Rosenblatt M: A mouse model of human breast cancer metastasis to human bone. Cancer Res. 2005, 65: 6130-6138. 10.1158/0008-5472.CAN-04-1408.CrossRefPubMed
44.
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
45.
Cowin P, Rowlands TM, Hatsell SJ: Cadherins and catenins in breast cancer. Curr Opin Cell Biol. 2005, 17: 499-508. 10.1016/j.ceb.2005.08.014.CrossRefPubMed
46.
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: 14228-14233. 10.1073/pnas.0400067101.CrossRefPubMedPubMedCentral
47.
Locke M, Heywood M, Fawell S, Mackenzie IC: Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines. Cancer Res. 2005, 65: 8944-8950. 10.1158/0008-5472.CAN-05-0931.CrossRefPubMed
48.
Sleeman KE, Kendrick H, Ashworth A, Isacke CM, Smalley MJ: CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Res. 2006, 8: R7-10.1186/bcr1371.CrossRefPubMed
49.
Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE: Generation of a functional mammary gland from a single stem cell. Nature. 2006, 439: 84-88. 10.1038/nature04372.CrossRefPubMed
50.
Langlois AJ, Holder WD, Iglehart JD, Nelson-Rees WA, Wells SA, Bolognesi DP: Morphological and biochemical properties of a new human breast cancer cell line. Cancer Res. 1979, 39: 2604-2613.PubMed
51.
Gaffney EV: A cell line (HBL-100) established from human breast milk. Cell Tissue Res. 1982, 227: 563-568. 10.1007/BF00204786.CrossRefPubMed
52.
Soule HD, Maloney TM, Wolman SR, Peterson WD, Brenz R, McGrath CM, Russo J, Pauley RJ, Jones RF, Brooks SC: Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res. 1990, 50: 6075-6086.PubMed
Metadata
Title
CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis
Authors
Carol Sheridan
Hiromitsu Kishimoto
Robyn K Fuchs
Sanjana Mehrotra
Poornima Bhat-Nakshatri
Charles H Turner
Robert Goulet Jr
Sunil Badve
Harikrishna Nakshatri
Publication date
01-10-2006
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2006
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1610

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