Skip to main content

Advertisement

SpringerLink
Log in

Interactions between breast cancer cells and bone marrow derived cells in vitro define a role for osteopontin in affecting breast cancer cell migration

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

The preferential metastasis of breast cancer cells to bone is a complex set of events including homing and preferential growth which may include unique factors produced by bone cells in the immediate microenvironment. In this study, we evaluated the suitability of bone cells derived from orthoplastic surgeries for use in an in vitro co-culture system representing a model of the bone microenvironment. Using a limiting dilution assay we determined the relative survival and proliferation potentials of breast cancer cell lines co-cultured on bone-derived cells or on Hs68 fibroblasts. The comparison of bone and skin fibroblastic substrata indicates that MCF-7 cells preferentially survive and grow in a bone microenvironment (P < 0.001). Overall, we show that bone-derived cells enhance survival, proliferation, and migration of breast cancer cells, where migration is in part mediated by bone cell-produced osteopontin. Our in vitro co-culture model system provides a robust cost-effective method to study the various factors that mediate cancer/bone-derived cell interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55:61–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fokas E, Engenhart-Cabillic R, Daniilidis K, Rose F, An HX (2007) Metastasis: the seed and soil theory gains identity. Cancer Metastasis Rev 26:705–715

    Article  PubMed  Google Scholar 

  3. Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584–593

    Article  CAS  PubMed  Google Scholar 

  4. Rabbani SA, Mazar AP (2007) Evaluating distant metastases in breast cancer: from biology to outcomes. Cancer Metastasis Rev 26:663–674

    Article  PubMed  Google Scholar 

  5. Paget S (1889) The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev 8:98–101

    Google Scholar 

  6. Kaplan RN, Psaila B, Lyden D (2006) Bone marrow cells in the ‘pre-metastatic niche’: within bone and beyond. Cancer Metastasis Rev 25:521–529

    Article  PubMed  Google Scholar 

  7. Tuck AB, Chambers AF (2001) The role of osteopontin in breast cancer: clinical and experimental studies. J Mammary Gland Biol Neoplasia 6:419–429

    Article  CAS  PubMed  Google Scholar 

  8. Cook AC et al (2005) Osteopontin induces multiple changes in gene expression that reflect the six “hallmarks of cancer” in a model of breast cancer progression. Mol Carcinog 43:225–236

    Article  CAS  PubMed  Google Scholar 

  9. Coppola D et al (2004) Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res 10:184–190

    Article  CAS  PubMed  Google Scholar 

  10. Rudland PS et al (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 62:3417–3427

    CAS  PubMed  Google Scholar 

  11. Fedarko NS, Jain A, Karadag A (2001) Van Eman, M.R. & Fisher, L.W. Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res 7:4060–4066

    CAS  PubMed  Google Scholar 

  12. Tuck AB, Elliott BE, Hota C, Tremblay E, Chambers AF (2000) Osteopontin-induced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor (Met). J Cell Biochem 78:465–475

    Article  CAS  PubMed  Google Scholar 

  13. Singhal H et al (1997) Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clin Cancer Res 3:605–611

    CAS  PubMed  Google Scholar 

  14. Tuck AB et al (1999) Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 18:4237–4246

    Article  CAS  PubMed  Google Scholar 

  15. Furger KA, Menon RK, Tuck AB, Bramwell VH, Chambers AF (2001) The functional and clinical roles of osteopontin in cancer and metastasis. Curr Mol Med 1:621–632

    Article  CAS  PubMed  Google Scholar 

  16. Chambers AF (2009) MDA-MB-435 and M14 cell lines: identical but not M14 melanoma? Cancer Res 69:5292–5293

    Article  CAS  PubMed  Google Scholar 

  17. Christgen M, Lehmann U (2007) MDA-MB-435: the questionable use of a melanoma cell line as a model for human breast cancer is ongoing. Cancer Biol Ther 6:1355–1357

    Article  CAS  PubMed  Google Scholar 

  18. Ellison G et al (2002) Further evidence to support the melanocytic origin of MDA-MB-435. Mol Pathol 55:294–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lacroix M (2009) MDA-MB-435 cells are from melanoma, not from breast cancer. Cancer Chemother Pharmacol 63:567

    Article  PubMed  Google Scholar 

  20. Rae JM, Creighton CJ, Meck JM, Haddad BR, Johnson MD (2007) MDA-MB-435 cells are derived from M14 melanoma cells—a loss for breast cancer, but a boon for melanoma research. Breast Cancer Res Treat 104:13–19

    Article  PubMed  Google Scholar 

  21. Ross DT et al (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet 24:227–235

    Article  CAS  PubMed  Google Scholar 

  22. Sellappan S et al (2004) Lineage infidelity of MDA-MB-435 cells: expression of melanocyte proteins in a breast cancer cell line. Cancer Res 64:3479–3485

    Article  CAS  PubMed  Google Scholar 

  23. Rastaldi MP et al (2002) Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int 62:137–146

    Article  PubMed  Google Scholar 

  24. Davila RM, Crouch EC (1993) Role of mesothelial and submesothelial stromal cells in matrix remodeling following pleural injury. Am J Pathol 142:547–555

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Lefkovits I, Waldmann H (1999) Limiting dilution analysis of cells of the immune system. Oxford University Press, New York

    Google Scholar 

  26. Laemmli K (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  27. Wagner W, Ho AD (2007) Mesenchymal stem cell preparations—comparing apples and oranges. Stem Cell Rev 3:239–248

    Article  PubMed  Google Scholar 

  28. Wagner W et al (2007) Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells 25:2638–2647

    Article  CAS  PubMed  Google Scholar 

  29. Kapoor P, Suva LJ, Welch DR, Donahue HJ (2008) Osteoprotegrin and the bone homing and colonization potential of breast cancer cells. J Cell Biochem 103:30–41

    Article  CAS  PubMed  Google Scholar 

  30. Mercer RR, Mastro AM (2005) Cytokines secreted by bone-metastatic breast cancer cells alter the expression pattern of f-actin and reduce focal adhesion plaques in osteoblasts through PI3 K. Exp Cell Res 310:270–281

    Article  CAS  PubMed  Google Scholar 

  31. Mazzali M et al (2002) Osteopontin—a molecule for all seasons. QJM 95:3–13

    Article  CAS  PubMed  Google Scholar 

  32. Denhardt DT, Guo X (1993) Osteopontin: a protein with diverse functions. FASEB J 7:1475–1482

    CAS  PubMed  Google Scholar 

  33. Rittling SR, Chambers AF (2004) Role of osteopontin in tumour progression. Br J Cancer 90:1877–1881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wai PY, Kuo PC (2004) The role of Osteopontin in tumor metastasis. J Surg Res 121:228–241

    Article  CAS  PubMed  Google Scholar 

  35. Giachelli CM, Steitz S (2000) Osteopontin: a versatile regulator of inflammation and biomineralization. Matrix Biol 19:615–622

    Article  CAS  PubMed  Google Scholar 

  36. Frolke JP et al (2004) Viable osteoblastic potential of cortical reamings from intramedullary nailing. J Orthop Res 22:1271–1275

    Article  PubMed  Google Scholar 

  37. Kaur D, Berger P, Duffy SM, Brightling CE, Bradding P (2005) Co-cultivation of mast cells and Fc epsilon RI alpha + dendritic-like cells from human hip bone marrow. Clin Exp Allergy 35:226–233

    Article  CAS  PubMed  Google Scholar 

  38. Tydings JD, Martino LJ, Kircher M, Alfred RH, Lozman J (1987) Viability of intramedullary canal bone reamings for continued calcification. Am J Surg 153:306–309

    Article  CAS  PubMed  Google Scholar 

  39. Lodie TA et al (2002) Systematic analysis of reportedly distinct populations of multipotent bone marrow-derived stem cells reveals a lack of distinction. Tissue Eng 8:739–751

    Article  CAS  PubMed  Google Scholar 

  40. Hughes L, Malone C, Chumsri S, Burger AM, McDonnell S (2008) Characterisation of breast cancer cell lines and establishment of a novel isogenic subclone to study migration, invasion and tumourigenicity. Clin Exp Metastasis 25:549–557

    Article  PubMed  Google Scholar 

  41. Plopper GE, Domanico SZ, Cirulli V, Kiosses WB, Quaranta V (1998) Migration of breast epithelial cells on Laminin-5: differential role of integrins in normal and transformed cell types. Breast Cancer Res Treat 51:57–69

    Article  CAS  PubMed  Google Scholar 

  42. Zhang X et al (2004) Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is associated with IRS-2 activation and integrin expression. Breast Cancer Res Treat 83:161–170

    Article  CAS  PubMed  Google Scholar 

  43. Rodrigues LR, Teixeira JA, Schmitt FL, Paulsson M, Lindmark-Mansson H (2007) The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol Biomarkers Prev 16:1087–1097

    Article  CAS  PubMed  Google Scholar 

  44. Noti JD (2000) Adherence to osteopontin via alphavbeta3 suppresses phorbol ester-mediated apoptosis in MCF-7 breast cancer cells that overexpress protein kinase C-alpha. Int J Oncol 17:1237–1243

    CAS  PubMed  Google Scholar 

  45. Tanabe KK, Nishi T, Saya H (1993) Novel variants of CD44 arising from alternative splicing: changes in the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells treated with hyaluronidase. Mol Carcinog 7:212–220

    Article  CAS  PubMed  Google Scholar 

  46. He B, Mirza M, Weber GF (2005) An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene 25:2192–2202

    Article  Google Scholar 

  47. Adwan H, Bauerle TJ, Berger MR (2004) Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells. Cancer Gene Ther 11:109–120

    Article  CAS  PubMed  Google Scholar 

  48. Bautista DS, Xuan JW, Hota C, Chambers AF, Harris JF (1994) Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin. J Biol Chem 269:23280–23285

    CAS  PubMed  Google Scholar 

  49. Denhardt DT, Noda M (1998) Osteopontin expression and function: role in bone remodeling. J Cell Biochem Suppl 30–31:92–102

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Gwyn Bebb and Dr. Frank Jirik for the gift of cell lines. Thanks also to Elizabeth Kornaga for help with the statistical analysis and Ravinder Singh for careful reading of the manuscript. Grant support: Alberta Cancer Board, Breast Cancer Operating Grant Project #23141. Canadian Breast Cancer Foundation – Prairies/NWT Chapter, Project “Development of Diagnostic and Therapeutic Agents that recognize a Mutated Form of Src Kinase in Breast Cancer”. Canadian Institutes of Health Research Studentship support for K. Koro. Translational Research Training in Cancer Program Studentship for K. Koro. Alberta Heritage Foundation for Medical Research and Alberta Cancer Research Institute summer studentship support for K. Koro, S. Parkin.

Conflict of interest statement

None of the authors have a conflict of interest.

Author information

Authors and Affiliations

  1. University of Calgary, Calgary, Canada

    Konstantin Koro, Stephen Parkin, Brant Pohorelic, An-Dao Yang, Aru Narendran, Cay Egan & Anthony Magliocco

Authors
  1. Konstantin Koro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen Parkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brant Pohorelic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. An-Dao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aru Narendran
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cay Egan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anthony Magliocco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cay Egan.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (EPS 2636 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koro, K., Parkin, S., Pohorelic, B. et al. Interactions between breast cancer cells and bone marrow derived cells in vitro define a role for osteopontin in affecting breast cancer cell migration. Breast Cancer Res Treat 126, 73–83 (2011). https://doi.org/10.1007/s10549-010-0889-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-010-0889-9

Keywords

Search

Navigation