Clinical & Experimental Metastasis

, Volume 17, Issue 3, pp 193–204 | Cite as

LCC15-MB: a vimentin-positive human breast cancer cell line from a femoral bone metastasis

  • E.W. Thompson
  • V. Sung
  • M. Lavigne
  • K. Baumann
  • N. Azumi
  • A.D. Aaron
  • R. Clarke

Abstract

The LCC15-MB cell line was established from a femoral bone metastasis that arose in a 29-year-old woman initially diagnosed with an infiltrating ductal mammary adenocarcinoma. The tumor had a relatively high (8%) S-phase fraction and 1/23 positive lymph nodes (LN). Both the primary tumor and LN metastasis were positive for estrogen receptor (ER) and progesterone receptor (PgR), but lacked erbB2 expression. Approximately one year later, the patient presented with a 0.8 cm comedo-type intraductal mammary adenocarcinoma in the left breast that was negative for ER and PgR, but positive for erbB2. Thirty-five months after the initial diagnosis she was treated for acute skeletal metastasis, and stabilized with a hip replacement. At this time, tumor cells were removed from surplus involved bone, inoculated into cell culture, and developed into the LCC15-MB cell line. The bone metastasis was a poorly differentiated adenocarcinoma lacking ER, PgR, and erbB2, characteristics shared by the LCC15-MB cells, although ER can be re-expressed by treatment of the LCC15-MB cells for 5 days with 75 μM 5-aza-2′-deoxycytidine. The LCC15-MB cell line is tumorigenic when implanted subcutaneously in NCr nu/nu mice and produces long-bone metastases after intracardiac injection. Although the bone metastasis from which the LCC15-MB cell line was derived lacked vimentin (VIM) expression, the original primary tumor and lymph node metastasis were strongly VIM positive, as are LCC15-MB cells in vitro and in nude mice. The karyotype and isozyme profiles of LCC15-MB cells are consistent with its origin from a human female, with most chromosome counts in the hypertriploid range. Thirty-two marker chromosomes are present. These cells provide an in vitro/in vivo model in which to study the inter-relationships between ER, VIM, and bone metastasis in human breast cancer.

bone metastasis cell line demethylation estrogen receptor human breast cancer vimentin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, CA Cancer J Clin 1997; 47: 5–27.Google Scholar
  2. 2.
    Cadman E, Bertino JR. Chemotherapy of skeletal metastases. Int J Radiat Oncol Biol Phys 1976; 1: 1211–5.Google Scholar
  3. 3.
    Drews M, Dickson RB. Osseous complications ofmalignancy. In Lockich JJ (ed) Clinical Cancer Medicine; Treatment Tactics. Boston: G.K. Hall 1980; 97–125.Google Scholar
  4. 4.
    Enneking WF. Metastatic Carcinoma; Musculoskeletal Tumor Surgery. New York: Churchill Livingstone 1983.Google Scholar
  5. 5.
    Harrington KD. Orthopedic Management ofMetastatic Bone Disease. St. Louis: Mosby 1988.Google Scholar
  6. 6.
    Wirth CR. Metastatic bone cancer. Curr Probl Cancer 1979; 3: 1–36.Google Scholar
  7. 7.
    Orr FW, Kostenuik P, Sanchez-Sweatman OH, Singh G. Mechanisms involved in the metastasis of cancer to bone. Breast Cancer Res Treat 1993; 25: 151–63.Google Scholar
  8. 8.
    Orr FW, Varani J, Gondek MD et al. Partial characterization of a bonederived chemotactic factor for tumor cells. Am J Pathol 1980; 99: 43–52.Google Scholar
  9. 9.
    Diel IJ, Kaufmann M, Costa SD et al. Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 1996; 88: 1652–8.Google Scholar
  10. 10.
    Yoneda T, Sasaki A, Mundy GR. Osteolytic bone metastasis in breast cancer. Breast Cancer Res Treat 1994; 32: 73–84.Google Scholar
  11. 11.
    Price JE, Polyzos A, Zhang RD, Daniels LM. Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice. Cancer Res 1990; 50: 717–21.Google Scholar
  12. 12.
    Price JE, Zhang RD. Studies of human breast cancer metastasis using nude mice. Cancer Metastasis Rev 1990; 8: 285–97.Google Scholar
  13. 13.
    Arguello F, Baggs RB, Frantz CN. A murine model of experimental metastasis to bone and bone marrow. Cancer Res 1988; 48: 6876–81.Google Scholar
  14. 14.
    Nakai M, Mundy GR, Williams PJ et al. A synthetic antagonist to laminin inhibits the formation of osteolytic metastases by human melanoma cells in nude mice. Cancer Res 1992; 52: 5395–9.Google Scholar
  15. 15.
    Sung V, Cattell DA, Bueno J et al. Human breast cancer cell metastasis to long bone and soft organs of nude mice: A quantitative assay. Clin Exp Metastasis 1997; 15: 173–83.Google Scholar
  16. 16.
    Mbalaviele G, Dunstan CR, Sasaki A et al. E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model. Cancer Res 1996; 56: 4063–70.Google Scholar
  17. 17.
    Sasaki A, Boyce BF, Story B et al. Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res 1995; 55: 3551–7.Google Scholar
  18. 18.
    Evans CE, Ward C, Braidman IP. Breast carcinomas synthesize factors which influence osteoblast-like cells independently of osteoclasts in vitro. J Endocrinol 1991; 128: R5–8.Google Scholar
  19. 19.
    Clohisy DR, Ogilvie CM, Ramnaraine ML. Tumor osteolysis in osteopetrotic mice. J Orthop Res 1995; 13: 892–7.Google Scholar
  20. 20.
    Ohishi K, Fujita N, Morinaga Y, Tsuruo T. H-31 human breast cancer cells stimulate type I collagenase production in osteoblast-like cells and induce bone resorption. Clin Exp Metastasis 1995; 13: 287–95.Google Scholar
  21. 21.
    Mundy GR, Yoneda T. Facilitation and suppression of bone metastasis. Clin Orthop 1995; 312: 34–44.Google Scholar
  22. 22.
    Engel LW, Young NA, Tralka TS et al. Establishment and characterization of three new continuous cell lines derived from human breast carcinomas. Cancer Res 1978; 38: 3352–64.Google Scholar
  23. 23.
    Clarke R, Leonessa F, Brunner N et al. In vitro models of human breast cancer. In: Harris JR, Lippman ME, Morrow M, Hellman (eds) Diseases of the Breast.New York: Lippincott, J.B., Co. 1995; 245–261.Google Scholar
  24. 24.
    Engel LW, Young NA. Human breast carcinoma cells in continuous culture: A review. Cancer Res 1978; 38: 4327–39.Google Scholar
  25. 25.
    Cailleau R, Olive M, Cruciger QV. Long-term human breast carcinoma cell lines of metastatic origin: Preliminary characterization. In Vitro 1978; 14: 911–5.Google Scholar
  26. 26.
    Robertson JF. Oestrogen receptor: a stable phenotype in breast cancer. Br J Cancer 1996; 73: 5–12.Google Scholar
  27. 27.
    Kaufmann M. Review of known prognostic variables. Recent Results Cancer Res 1996; 140: 77–87.Google Scholar
  28. 28.
    Gilles C, Thompson EW. The epithelial to mesenchymal transition and metastatic progression in carcinoma. The Breast Journal 1996; 2: 83-96.Google Scholar
  29. 29.
    Kulesh DA, Oshima RG. Cloning of the human keratin 18 gene and its expression in nonepithelial mouse cells. Mol Cell Biol 1988; 8: 1540–50.Google Scholar
  30. 30.
    Noguchi S, Aihara T, Motomura K et al. Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between muc1 mRNA and keratin 19 mRNA amplification. Am J Pathol 1996; 148: 649–56.Google Scholar
  31. 31.
    Clarke R, Morwood J, van den Berg HW et al. Effect of cytotoxic drugs on estrogen receptor expression and response to tamoxifen in MCF-7 cells. Cancer Res 1986; 46: 6116–9.Google Scholar
  32. 32.
    Ferguson AT, Lapidus RG, Baylin SB, Davidson NE. Demethylation of the estrogen receptor gene in estrogen receptor-negative breast cancer cells can reactivate estrogen receptor gene expression. Cancer Res 1995; 55:2279–83.Google Scholar
  33. 33.
    Thompson EW, Paik S, Brunner N 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: 534–44.Google Scholar
  34. 34.
    Sommers CL, Thompson EW, Torri JA et al. Cell adhesion molecule uvomorulin expression in human breast cancer cell lines: Relationship to morphology and invasive capacities. Cell Growth Differ 1991; 2: 365–72.Google Scholar
  35. 35.
    Sommers CL, Heckford SE, Skerker JM et al. Loss of epithelial markers and acquisition of vimentin expression in adriamycin-and vinblastine-resistant human breast cancer cell lines. Cancer Res 1992; 52: 5190–7.Google Scholar
  36. 36.
    Sommers CL, Byers SW, Thompson EW et al. Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res Treat 1994; 31: 325–35.Google Scholar
  37. 37.
    Bae SN, Arand G, Azzam H et al. Molecular and cellular analysis of basement membrane invasion by human breast cancer cells in matrigel-based in vitro assays. Breast Cancer Res Treat 1993; 24: 241–55.Google Scholar
  38. 38.
    Traweek ST, Liu J, Battifora H. Keratin gene expression in nonepithelial tissues. detection with polymerase chain reaction. Am J Pathol 1993; 142: 1111–8.Google Scholar
  39. 39.
    Datta YH, Adams PT, Drobyski WR et al. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol 1994; 12: 475–82.Google Scholar
  40. 40.
    Robertson JF, Dixon AR, Nicholson RI et al. Confirmation of a prognostic index for patients with metastatic breast cancer treated by endocrine therapy. Breast Cancer Res Treat 1992; 22: 221–7.Google Scholar
  41. 41.
    Clark GM, Sledge GW, Jr., Osborne CK, McGuireWL. Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients. J Clin Oncol 1987; 5: 55–61.Google Scholar
  42. 42.
    Koenders PG, Beex LV, Langens R et al. Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. The breast cancer study group. Breast Cancer Res Treat 1991; 18: 27–32.Google Scholar
  43. 43.
    Mano H, Yuasa T, Kameda T et al. Mammalian mature osteoclasts as estrogen target cells. Biochem Biophys Res Commun 1996; 223: 637–42.Google Scholar
  44. 44.
    Hoshino S, Inoue S, Hosoi T et al. Demonstration of isoforms of the estrogen receptor in the bone tissues and in osteoblastic cells. Calcif Tissue Int 1995; 57: 466–8.Google Scholar
  45. 45.
    Shen V, Birchman R, Xu R et al. Effects of reciprocal treatment with estrogen and estrogen plus parathyroid hormone on bone structure and strength in ovariectomized rats. J Clin Invest 1995; 96: 2331–8.Google Scholar
  46. 46.
    Lindsay R. The oestrogen receptor in bone-evolution of our knowledge. Br J Obstet Gynaecol 1996; 103: Suppl 13, 16–8; discussion 18- 9.Google Scholar
  47. 47.
    Dickson RB, Lippman ME. Growth factors in breast cancer. Endocr Rev 1995; 16: 559–89.Google Scholar
  48. 48.
    Allred DC, Clark GM, Molina R et al. Overexpression of Her-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 1992; 23: 974–9.Google Scholar
  49. 49.
    Allred DC, Clark GM, Tandon AK et al. Her-2/neu in node-negative breast cancer: Prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 1992; 10: 599–605.Google Scholar
  50. 50.
    Domagala W, Lasota J, Dukowicz A et al. Vimentin expression appears to be associated with poor prognosis in node-negative ductal NOS breast carcinomas. Am J Pathol 1990; 137: 1299–304.Google Scholar
  51. 51.
    Domagala W, Lasota J, Bartkowiak J et al. Vimentin is preferentially expressed in human breast carcinomas with low estrogen receptor and high Ki-67 growth fraction. Am J Pathol 1990; 136: 219–27.Google Scholar
  52. 52.
    Gilles C, Polette M, Piette J et al. Vimentin expression in cervical carcinomas:association with the invasive and the migratory phenotype of tumor cells. J Pathol 1996; 180: 175–180.Google Scholar
  53. 53.
    Savagner P, Boyer B, Valles AM et al. Modulations of the epithelial phenotype during embryogenesis and cancer progression. Cancer Treat Res 1994; 71: 229–49.Google Scholar
  54. 54.
    Iwaya K, Thompson EW, Azumi N. Vimentin expression is a predictor of early recurrence and death in node negative carcinoma patients [Abstract].Mod Pathol 1995; 8: 19A.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • E.W. Thompson
    • 1
    • 5
  • V. Sung
    • 1
  • M. Lavigne
    • 2
  • K. Baumann
    • 3
  • N. Azumi
    • 3
  • A.D. Aaron
    • 4
  • R. Clarke
    • 2
  1. 1.Vincent T. Lombardi Cancer Center, and Departments of Cell BiologyGeorgetown University Medical CenterWashingtonUSA
  2. 2.Vincent T. Lombardi Cancer Center, PhysiologyGeorgetown University Medical CenterWashingtonUSA
  3. 3.Vincent T. Lombardi Cancer Center, and Departments of PathologyGeorgetown University Medical CenterWashingtonUSA
  4. 4.Vincent T. Lombardi Cancer Center, and Departments of Orthopaedic SurgeryGeorgetown University Medical CenterWashingtonUSA
  5. 5.St. Vincent's Institute of Medical ResearchUniversity of MelbourneFitzroyAustralia

Personalised recommendations