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Differentiation state and invasiveness of human breast cancer cell lines

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Summary

Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and β1 and β4 integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47DCO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.

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References

  1. Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–377, 1957

    Google Scholar 

  2. Stenkvist B, Bengtsson E, Dahlqvist B, Eklund G, Eriksson O, Jarkrans T, Nordin B: Predicting breast cancer recurrence. Cancer 50: 2884–2893, 1982

    Google Scholar 

  3. Takeichi M: Cadherins: a molecular family important in selective cell-cell adhesion. Annu Rev Biochem 59: 237–252, 1990

    Google Scholar 

  4. Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, Takatsuka Y, Matsuyoshi N, Hirano S, Takeichi M, Mori T: Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res 53: 1696–1701, 1993

    Google Scholar 

  5. Gamallo C, Palacios J, Suarez A, Pizarro A, Navarro P, Quintanilla M, Cano A: Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol 142: 987–993, 1993

    Google Scholar 

  6. Rasbridge SA, Gillett CE, Sampson SA, Walsh FS, Millis RR: Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma. J Pathol 169: 245–250, 1993

    Google Scholar 

  7. Pignatelli M, Cardillo MR, Hanby A, Stamp GWH: Integrins and their accessory adhesion molecules in mammary carcinomas: loss of polarization in poorly differentiated tumors. Hum Pathol 23: 1159–1166, 1992

    Google Scholar 

  8. Zutter MM, Mazoujian G, Santoro SA: Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast. Am J Pathol 137: 863–870, 1990

    Google Scholar 

  9. Jones JL, Critchley DR, Walker RA: Alteration of stromal protein and integrin expression in breast-a marker of premalignant change? J Pathol 167: 399–406, 1992

    Google Scholar 

  10. Pignatelli M, Hanby AM, Stamp GWH: Low expression of beta-1, alpha-2 and alpha-3 subunits of VLA integrins in malignant mammary tumours. J Pathol 165: 25–32, 1991

    Google Scholar 

  11. Koukoulis GK, Virtanen I, Korhonen M, Laitinen L, Quaranta V, Gould VE: Immunohistochemical localization of integrins in the normal, hyperplastic, and neoplastic breast. Am J Pathol 4: 787–799, 1991

    Google Scholar 

  12. Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, Birchmeier W, Funke I: E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53: 1690–1695, 1993

    Google Scholar 

  13. Schipper JH, Frixen UH, Behrens J, Unger A, Jahnke K, Birchmeier W: E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res 51: 6328–6337, 1991

    Google Scholar 

  14. Umbas R, Schalken JA, Aalders TW, Carter BS, Karthaus HF, Schaafsma HE, Debruyne FM, Isaacs WB: Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. Cancer Res 52: 5104–5109, 1992

    Google Scholar 

  15. Dorudi S, Sheffield JP, Poulsom R, Northover JM, Hart IR: E-cadherin expression in colorectal cancer. An immunocytochemical andin situ hybridization study. Am J Pathol 142: 981–986, 1993

    Google Scholar 

  16. Bringuier PP, Umbas R, Schaafsma HE, Karthaus HFM, Debruyne FMJ, Schalken JA: Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res 53: 3241–3245, 1993

    Google Scholar 

  17. Harada T, Shinohara M, Nakamura S, Shimada M, Oka M: Immunohistochemical detection of desmosomes in oral squamous cell carcinomas: correlation with dedifferentiation, mode of invasion, and metastatic potential. Int J Oral Maxillofac Surg 21: 346–349, 1992

    Google Scholar 

  18. Lee SW, Tomasetto C, Paul D, Keyomarsi K, Sager R: Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines. J Cell Biol 118: 1213–1221, 1992

    Google Scholar 

  19. Bernal SD, Stahel RA: Cytoskeleton-associated proteins: their role as cellular integrators in the neoplastic process. CRC Crit Rev Oncol Hematol 3: 191–204, 1985

    Google Scholar 

  20. Sommers CL, Walker-Jones D, Heckford SE, Worland P, Valverius E, Clark R, McCormick F, Stampfer M, Abularach S, Gelmann EP: Vimentin rather than keratin expression in some hormone-independent breast cancer cell lines and in oncogene-transformed mammary epithelial cells. Cancer Res 49: 4258–4263, 1989

    Google Scholar 

  21. Thompson EW, Paik S, Brunner N, Sommers CL, Zugmaier G, Clarke R, Shima TB, Torri J, Donohue S, Lippman ME, Martin GR, Dickson RB: Association of increased basement membrane-invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J Cell Physiol 150: 534–544, 1992

    Google Scholar 

  22. Heatley M, Whiteside C, Maxwell P, Toner P: Vimentin expression in benign and malignant breast epithelium. J Clin Pathol 46: 441–445, 1993

    Google Scholar 

  23. Domagala W, Lasota J, Bartowiak J, Weber K, Osborn M: Vimentin is preferentially expressed in human breast carcinomas with low estrogen receptor and high Ki-67 growth fraction. Am J Pathol 136: 219–227, 1990

    Google Scholar 

  24. Domagala W, Leszek W, Lasota J, Weber K, Osborn M: Vimentin is preferentially expressed in high-grade ductal and medullary, but not in lobular breast carcinomas. Am J Pathol 137: 1059–1064, 1990

    Google Scholar 

  25. Raymond WA, Leong AS-Y: Vimentin - A new prognostic parameter in breast carcinoma? J Pathol 158: 107–114, 1989

    Google Scholar 

  26. Cattoretti G, Andreola S, Clemente C, D'Amato L, Rilke F: Vimentin and p53 expression on epidermal growth factor receptor-positive, oestrogen receptor-negative breast carcinomas. Br J Cancer 57: 353–357, 1988

    Google Scholar 

  27. Gould VE, Kouloulis GK, Jansson DS, Nagle RB, Franke WW, Moll R: Coexpression patterns of vimentin and glial filament protein with cytokeratins in the normal, hyperplastic, and neoplastic breast. Am J Pathol 137: 1143–1155, 1990

    Google Scholar 

  28. Wada T, Yasutomi M, Hashmura K, Kunikata M, Tanaka T, Mori M: Vimentin expression in benign and malignant lesions in the human mammary gland. Anticancer Res 122: 1973–1982, 1992

    Google Scholar 

  29. Azumi N, Battifora H: The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. Am J Clin Pathol 188: 286–296, 1987

    Google Scholar 

  30. Sommers CL, Thompson EW, Torri JA, Kemler R, Gelmann EP, Byers SW: Cell adhesion molecule uvomorulin expression in human breast cancer cell lines: relationship to morphology and invasive capacities. Cell Growth and Diff 2: 365–372, 1991

    Google Scholar 

  31. Van Waes C, Kozarsky KF, Warren AB, Kidd L, Paugh D, Liebert M, Carey TE: The A9 antigen associated with aggressive human squamous carcinoma is structurally and functionally similar to the newly defined integrin alpha 6 beta 4. Cancer Res 51: 2395–2402, 1991

    Google Scholar 

  32. Tait L, Soule HD, Russo J: Ultrastructural and immunocytochemical characterization of an immortalized human breast epithelial cell line, MCF-10. Cancer Res 50: 6087–6094, 1990

    Google Scholar 

  33. Graham ML, Krett NL, Miller LA, Leslie KK, Gordon DF, Wood WM, Wei LL, Horwitz KB: T47Dco cells, genetically unstable and containing estrogen receptor mutations, are a model for the progression of breast cancers to hormone resistance. Cancer Res 50: 6208–6217, 1990

    Google Scholar 

  34. Sommers CL, Heckford SE, Skerker JM, Worland P, Torri J, Thompson EW, Byers SW, Gelmann EP: Loss of epithelial markers and acquisition of vimentin expression in adriamycin-and vinblastine-resistant human breast cancer cell lines. Cancer Research 52: 5190–5197, 1992

    Google Scholar 

  35. Behrens J, Mareel MM, Van Roy FM, Birchmeier W: Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol 108: 2435–2447, 1989

    Google Scholar 

  36. Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Lochner D, Birchmeier W: E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 113: 173–185, 1991

    Google Scholar 

  37. Chen WC, Obrink B: Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells. J Cell Biol 114: 319–327, 1991

    Google Scholar 

  38. Vleminckx K, Vakaet L, Mareel M, Fiers W, Van Roy F: Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 66: 107–119, 1991

    Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology and the Vincent T. Lombardi Cancer Research Center, Georgetown University, 20007, Washington, DC, USA

    Connie L. Sommers, Stephen W. Byers, Erik W. Thompson, Jeffrey A. Torri & Edward P. Gelmann

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  1. Connie L. Sommers
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  2. Stephen W. Byers
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  3. Erik W. Thompson
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  4. Jeffrey A. Torri
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  5. Edward P. Gelmann
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Sommers, C.L., Byers, S.W., Thompson, E.W. et al. Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res Tr 31, 325–335 (1994). https://doi.org/10.1007/BF00666165

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