Skip to main content

Advertisement

SpringerLink
Log in

Role of Src in breast cancer cell migration and invasion in a breast cell/bone-derived cell microenvironment

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

An Erratum to this article was published on 11 October 2011

Abstract

The preferential metastasis of breast cancer cells to bone comprises a complex set of events including homing and preferential growth, which may require unique factors produced by bone or other cells in the immediate microenvironment. In this study, an in vitro co-culture system composed of bone mesenchymal stem cells and breast cancer cell lines is used to examine the role of Src kinase on breast cancer cell migration and invasion in the presence of bone-derived cells. This research shows that Src kinase activity in breast cancer cell lines with either high or low levels of endogenous Src activity is increased by bone-derived cell-conditioned medium but not HS68 fibroblast-conditioned medium. Breast cancer cells exhibit enhanced migration in co-culture with bone-derived cells but not HS68 fibroblasts or no co-cultured cells. Inhibition of Src kinase activity using the inhibitors PP2 or saracatinib or using siRNA abrogates the preferential migration of the breast cancer cell lines in response to bone-derived cells. Inhibition of Src activity with saracatinib does not have any significant effect on breast cancer cell invasion in the presence of bone-derived cells. Factors are identified that are produced preferentially by bone-derived cells over HS68 cells that may impact breast cancer cell behavior. This research implicates Src kinase as an important effector of bone-derived cell signals on breast cancer cell migration.

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. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin. doi:10.3322/caac.20107

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

    Article  PubMed  CAS  Google Scholar 

  3. Coleman RE, Smith P, Rubens RD (1998) Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer 77(2):336–340

    Article  PubMed  CAS  Google Scholar 

  4. Fokas E, Engenhart-Cabillic R, Daniilidis K, Rose F, An HX (2007) Metastasis: the seed and soil theory gains identity. Cancer Metastasis Rev 26(3–4):705–715. doi:10.1007/s10555-007-9088-5

    Article  PubMed  Google Scholar 

  5. Mundy GR (2002) Metastasis to bone: causes, consequences, and therapeutic opportunities. Nat Rev Cancer 2(8):584–593. doi:10.1038/nrc867

    Article  PubMed  CAS  Google Scholar 

  6. Rabbani SA, Mazar AP (2007) Evaluating distant metastases in breast cancer: from biology to outcomes. Cancer Metastasis Rev 26(3–4):663–674. doi:10.1007/s10555-007-9085-8

    Article  PubMed  Google Scholar 

  7. Paget S (1889) The distribution of secondary growths in cancer of the breast. Canc Metastasis Rev 8:98

    Google Scholar 

  8. Fidler IJ (1970) Metastasis: guantitative analysis of distribution and fate of tumor embolilabeled with 125 I-5-iodo-2′-deoxyuridine. J Natl Cancer Inst 45(4):773–782

    PubMed  CAS  Google Scholar 

  9. Fidler IJ, Nicolson GL (1977) Fate of recirculating B16 melanoma metastatic variant cells in parabiotic syngeneic recipients. J Natl Cancer Inst 58(6):1867–1872

    PubMed  CAS  Google Scholar 

  10. Klein CA, Seidl S, Petat-Dutter K, Offner S, Geigl JB, Schmidt-Kittler O, Wendler N, Passlick B, Huber RM, Schlimok G, Baeuerle PA, Riethmuller G (2002) Combined transcriptome and genome analysis of single micrometastatic cells. Nat Biotechnol 20(4):387–392. doi:10.1038/nbt0402-387

    Article  PubMed  CAS  Google Scholar 

  11. Morgan TM, Lange PH, Porter MP, Lin DW, Ellis WJ, Gallaher IS, Vessella RL (2009) Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence. Clin Cancer Res 15(2):677–683. doi:10.1158/1078-0432.CCR-08-1754

    Article  PubMed  CAS  Google Scholar 

  12. Pantel K, Schlimok G, Braun S, Kutter D, Lindemann F, Schaller G, Funke I, Izbicki JR, Riethmuller G (1993) Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J Natl Cancer Inst 85(17):1419–1424

    Article  PubMed  CAS  Google Scholar 

  13. Riethdorf S, Wikman H, Pantel K (2008) Review: biological relevance of disseminated tumor cells in cancer patients. Int J Cancer 123(9):1991–2006. doi:10.1002/ijc.23825

    Article  PubMed  CAS  Google Scholar 

  14. Huober J, Thurlimann B (2010) Bone targeted therapy in breast cancer: present and future. Crit Rev Oncol Hematol 74(1):S7–S10. doi:10.1016/S1040-8428(10)70004-4

    Article  PubMed  Google Scholar 

  15. Rose AA, Siegel PM (2010) Emerging therapeutic targets in breast cancer bone metastasis. Future Oncol 6(1):55–74. doi:10.2217/fon.09.138

    Article  PubMed  CAS  Google Scholar 

  16. Albanese I, Scibetta AG, Migliavacca M, Russo A, Bazan V, Tomasino RM, Colomba P, Tagliavia M, La Farina M (2004) Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations. Biochem Biophys Res Commun 325(3):784–791. doi:10.1016/j.bbrc.2004.10.111

    Article  PubMed  CAS  Google Scholar 

  17. Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ, Yang CH, Lee YC, Yang PC, Shih JY (2009) Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol 20(4):696–702. doi:10.1093/annonc/mdn679

    Article  PubMed  Google Scholar 

  18. Stoecklein NH, Klein CA (2010) Genetic disparity between primary tumours, disseminated tumour cells, and manifest metastasis. Int J Cancer 126(3):589–598. doi:10.1002/ijc.24916

    Article  PubMed  CAS  Google Scholar 

  19. Tortola S, Steinert R, Hantschick M, Peinado MA, Gastinger I, Stosiek P, Lippert H, Schlegel W, Reymond MA (2001) Discordance between K-ras mutations in bone marrow micrometastases and the primary tumor in colorectal cancer. J Clin Oncol 19(11):2837–2843

    PubMed  CAS  Google Scholar 

  20. Amir E, Ooi WS, Simmons C, Kahn H, Christakis M, Popovic S, Kalina M, Chesney A, Singh G, Clemons M (2008) Discordance between receptor status in primary and metastatic breast cancer: an exploratory study of bone and bone marrow biopsies. Clin Oncol (R Coll Radiol) 20(10):763–768. doi:10.1016/j.clon.2008.08.005

    Article  CAS  Google Scholar 

  21. Broom RJ, Tang PA, Simmons C, Bordeleau L, Mulligan AM, O’Malley FP, Miller N, Andrulis IL, Brenner DM, Clemons MJ (2009) Changes in estrogen receptor, progesterone receptor and Her-2/neu status with time: discordance rates between primary and metastatic breast cancer. Anticancer Res 29(5):1557–1562

    PubMed  Google Scholar 

  22. Koro K, Parkin S, Pohorelic B, Yang AD, Narendran A, Egan C, Magliocco A (2010) 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. doi:10.1007/s10549-010-0889-9

  23. Wheeler DL, Iida M, Dunn EF (2009) The role of Src in solid tumors. Oncologist 14(7):667–678. doi:10.1634/theoncologist.2009-0009

    Article  PubMed  CAS  Google Scholar 

  24. Kim LC, Song L, Haura EB (2009) Src kinases as therapeutic targets for cancer. Nat Rev Clin Oncol 6(10):587–595. doi:10.1038/nrclinonc.2009.129

    Article  PubMed  Google Scholar 

  25. Morgan L, Nicholson RI, Hiscox S (2008) SRC as a therapeutic target in breast cancer. Endocr Metab Immune Disord Drug Targets 8(4):273–278

    Article  PubMed  CAS  Google Scholar 

  26. Hilbig A (2008) Src kinase and pancreatic cancer. Recent Results Cancer Res 177:179–185

    Article  PubMed  CAS  Google Scholar 

  27. Chang YM, Bai L, Liu S, Yang JC, Kung HJ, Evans CP (2008) Src family kinase oncogenic potential and pathways in prostate cancer as revealed by AZD0530. Oncogene 27(49):6365–6375. doi:10.1038/onc.2008.250

    Article  PubMed  CAS  Google Scholar 

  28. Planas-Silva MD, Bruggeman RD, Grenko RT, Stanley Smith J (2006) Role of c-Src and focal adhesion kinase in progression and metastasis of estrogen receptor-positive breast cancer. Biochem Biophys Res Commun 341(1):73–81. doi:10.1016/j.bbrc.2005.12.164

    Article  PubMed  CAS  Google Scholar 

  29. Hiscox S, Morgan L, Green TP, Barrow D, Gee J, Nicholson RI (2006) Elevated Src activity promotes cellular invasion and motility in tamoxifen resistant breast cancer cells. Breast Cancer Res Treat 97(3):263–274

    Article  PubMed  CAS  Google Scholar 

  30. Hiscox S, Morgan L, Green T, Nicholson RI (2006) Src as a therapeutic target in anti-hormone/anti-growth factor-resistant breast cancer. Endocr Relat Cancer 13(1):S53–S59

    Article  PubMed  CAS  Google Scholar 

  31. Myoui A, Nishimura R, Williams PJ, Hiraga T, Tamura D, Michigami T, Mundy GR, Yoneda T (2003) C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. Cancer Res 63(16):5028–5033

    PubMed  CAS  Google Scholar 

  32. Frame MC (2002) Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta 1602(2):114–130

    PubMed  CAS  Google Scholar 

  33. Zambuzzi WF, Milani R, Teti A (2010) Expanding the role of Src and protein tyrosine phosphatases balance in modulating osteoblast metabolism: lessons from mice. Biochimie. doi:10.1016/j.biochi.2010.01.002

  34. Zambuzzi WF, Milani R, Teti A (2010) Expanding the role of Src and protein-tyrosine phosphatases balance in modulating osteoblast metabolism: lessons from mice. Biochimie 92(4):327–332. doi:10.1016/j.biochi.2010.01.002

    Article  PubMed  CAS  Google Scholar 

  35. de Vries TJ, Mullender MG, van Duin MA, Semeins CM, James N, Green TP, Everts V, Klein-Nulend J (2009) The Src inhibitor AZD0530 reversibly inhibits the formation and activity of human osteoclasts. Mol Cancer Res 7(4):476–488. doi:10.1158/1541-7786.MCR-08-0219

    Article  PubMed  Google Scholar 

  36. Zou W, Kitaura H, Reeve J, Long F, Tybulewicz VL, Shattil SJ, Ginsberg MH, Ross FP, Teitelbaum SL (2007) Syk, c-Src, the alphavbeta3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption. J Cell Biol 176(6):877–888. doi:10.1083/jcb.200611083

    Article  PubMed  CAS  Google Scholar 

  37. Miyazaki T, Sanjay A, Neff L, Tanaka S, Horne WC, Baron R (2004) Src kinase activity is essential for osteoclast function. J Biol Chem 279(17):17660–17666

    Article  PubMed  CAS  Google Scholar 

  38. Liu X, Feng R (2010) Inhibition of epithelial to mesenchymal transition in metastatic breast carcinoma cells by c-Src suppression. Acta Biochim Biophys Sin (Shanghai) 42(7):496–501. doi:10.1093/abbs/gmq043

    Article  CAS  Google Scholar 

  39. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, Foekens JA, Massague J (2009) Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16(1):67–78. doi:10.1016/j.ccr.2009.05.017

    Article  PubMed  CAS  Google Scholar 

  40. Sgroi DC (2009) Breast cancer SRC activity: bad to the bone. Cancer Cell 16(1):1–2. doi:10.1016/j.ccr.2009.06.010

    Article  PubMed  CAS  Google Scholar 

  41. Saad F, Lipton A (2010) SRC kinase inhibition: targeting bone metastases and tumor growth in prostate and breast cancer. Cancer Treat Rev 36(2):177–184. doi:10.1016/j.ctrv.2009.11.005

    Article  PubMed  CAS  Google Scholar 

  42. Hiscox S, Barrett-Lee P, Borley AC, Nicholson RI (2010) Combining Src inhibitors and aromatase inhibitors: a novel strategy for overcoming endocrine resistance and bone loss. Eur J Cancer. doi:10.1016/j.ejca.2010.04.012

  43. Araujo J, Logothetis C (2010) Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors. Cancer Treat Rev. doi: 10.1016/j.ctrv.2010.02.015

  44. Schweppe RE, Kerege AA, French JD, Sharma V, Grzywa RL, Haugen BR (2009) Inhibition of Src with AZD0530 reveals the Src-focal adhesion kinase complex as a novel therapeutic target in papillary and anaplastic thyroid cancer. J Clin Endocrinol Metab 94(6):2199–2203. doi:10.1210/jc.2008-2511

    Article  PubMed  CAS  Google Scholar 

  45. Rajeshkumar NV, Tan AC, De Oliveira E, Womack C, Wombwell H, Morgan S, Warren MV, Walker J, Green TP, Jimeno A, Messersmith WA, Hidalgo M (2009) Antitumor effects and biomarkers of activity of AZD0530, a Src inhibitor, in pancreatic cancer. Clin Cancer Res 15(12):4138–4146. doi:10.1158/1078-0432.CCR-08-3021

    Article  PubMed  CAS  Google Scholar 

  46. Purnell PR, Mack PC, Tepper CG, Evans CP, Green TP, Gumerlock PH, Lara PN, Gandara DR, Kung HJ, Gautschi O (2009) The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells. J Thorac Oncol 4(4):448–454. doi:10.1097/JTO.0b013e31819c78fb

    Article  PubMed  Google Scholar 

  47. Rucci N, Susa M, Teti A (2008) Inhibition of protein kinase c-Src as a therapeutic approach for cancer and bone metastases. Anticancer Agents Med Chem 8(3):342–349

    Article  PubMed  CAS  Google Scholar 

  48. Hiscox S, Nicholson RI (2008) Src inhibitors in breast cancer therapy. Expert Opin Ther Targets 12(6):757–767. doi:10.1517/14728222.12.6.757

    Article  PubMed  CAS  Google Scholar 

  49. Lee D, Gautschi O (2006) Clinical development of SRC tyrosine kinase inhibitors in lung cancer. Clin Lung Cancer 7(6):381–384

    Article  PubMed  CAS  Google Scholar 

  50. Zheng R, Yano S, Matsumori Y, Nakataki E, Muguruma H, Yoshizumi M, Sone S (2005) SRC tyrosine kinase inhibitor, m475271, suppresses subcutaneous growth and production of lung metastasis via inhibition of proliferation, invasion, and vascularization of human lung adenocarcinoma cells. Clin Exp Metastasis 22(3):195–204

    Article  PubMed  CAS  Google Scholar 

  51. Bagrodia S, Chackalaparampil I, Kmiecik TE, Shalloway D (1991) Altered tyrosine 527 phosphorylation and mitotic activation of p60c-src. Nature 349(6305):172–175

    Article  PubMed  CAS  Google Scholar 

  52. Bjorge JD, Jakymiw A, Fujita DJ (2000) Selected glimpses into the activation and function of Src kinase. Oncogene 19(49):5620–5635

    Article  PubMed  CAS  Google Scholar 

  53. Bjorge JD, O’Connor TJ, Fujita DJ (1996) Activation of human pp60c-src. Biochem Cell Biol 74(4):477–484

    Article  PubMed  CAS  Google Scholar 

  54. Cartwright CA, Kamps MP, Meisler AI, Pipas JM, Eckhart W (1989) pp60c-src activation in human colon carcinoma. J Clin Invest 83(6):2025–2033. doi:10.1172/JCI114113

    Article  PubMed  CAS  Google Scholar 

  55. Cooper JA, Howell B (1993) The when and how of Src regulation. Cell 73(6):1051–1054

    Article  PubMed  CAS  Google Scholar 

  56. Guarino M (2010) Src signaling in cancer invasion. J Cell Physiol 223(1):14–26. doi:10.1002/jcp.22011

    PubMed  CAS  Google Scholar 

  57. Superti-Furga G, Courtneidge SA (1995) Structure–function relationships in Src family and related protein tyrosine kinases. Bioessays 17(4):321–330

    Article  PubMed  CAS  Google Scholar 

  58. Green TP, Fennell M, Whittaker R, Curwen J, Jacobs V, Allen J, Logie A, Hargreaves J, Hickinson DM, Wilkinson RW, Elvin P, Boyer B, Carragher N, Ple PA, Bermingham A, Holdgate GA, Ward WH, Hennequin LF, Davies BR, Costello GF (2009) Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol. doi:10.1016/j.molonc.2009.01.002

  59. Previdi S, Maroni P, Matteucci E, Broggini M, Bendinelli P, Desiderio MA (2010) Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways. Eur J Cancer 46(9):1679–1691. doi:10.1016/j.ejca.2010.02.036

    Article  PubMed  CAS  Google Scholar 

  60. Coskun U, Gunel N, Sancak B, Gunel U, Onuk E, Bayram O, Yilmaz E, Candan S, Ozkan S (2003) Significance of serum vascular endothelial growth factor, insulin-like growth factor-I levels and nitric oxide activity in breast cancer patients. Breast 12(2):104–110

    Article  PubMed  Google Scholar 

  61. Coskun U, Gunel N, Toruner FB, Sancak B, Onuk E, Bayram O, Cengiz O, Yilmaz E, Elbeg S, Ozkan S (2003) Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer. Neoplasma 50(1):41–46

    PubMed  CAS  Google Scholar 

  62. Ahmed OI, Adel AM, Diab DR, Gobran NS (2006) Prognostic value of serum level of interleukin-6 and interleukin-8 in metastatic breast cancer patients. Egypt J Immunol 13(2):61–68

    PubMed  Google Scholar 

  63. Bendre MS, Gaddy-Kurten D, Mon-Foote T, Akel NS, Skinner RA, Nicholas RW, Suva LJ (2002) Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo. Cancer Res 62(19):5571–5579

    PubMed  CAS  Google Scholar 

  64. Benoy IH, Salgado R, Van Dam P, Geboers K, Van Marck E, Scharpe S, Vermeulen PB, Dirix LY (2004) Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival. Clin Cancer Res 10(21):7157–7162. doi:10.1158/1078-0432.CCR-04-0812

    Article  PubMed  CAS  Google Scholar 

  65. Salgado R, Junius S, Benoy I, Van Dam P, Vermeulen P, Van Marck E, Huget P, Dirix LY (2003) Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer 103(5):642–646. doi:10.1002/ijc.10833

    Article  PubMed  CAS  Google Scholar 

  66. Sasser AK, Sullivan NJ, Studebaker AW, Hendey LF, Axel AE, Hall BM (2007) Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J 21(13):3763–3770. doi:10.1096/fj.07-8832com

    Article  PubMed  CAS  Google Scholar 

  67. Zhang GJ, Adachi I (1999) Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res 19(2B):1427–1432

    PubMed  CAS  Google Scholar 

  68. Chan PC, Chen YL, Cheng CH, Yu KC, Cary LA, Shu KH, Ho WL, Chen HC (2003) Src phosphorylates Grb2-associated binder 1 upon hepatocyte growth factor stimulation. J Biol Chem 278(45):44075–44082. doi:10.1074/jbc.M305745200

    Article  PubMed  CAS  Google Scholar 

  69. Crostella L, Lidder S, Williams R, Skouteris GG (2001) Hepatocyte growth factor/scatter factor-induces phosphorylation of cortactin in A431 cells in a Src kinase-independent manner. Oncogene 20(28):3735–3745. doi:10.1038/sj.onc.1204474

    Article  PubMed  CAS  Google Scholar 

  70. Matteucci E, Ridolfi E, Maroni P, Bendinelli P, Desiderio MA (2007) c-Src/histone deacetylase 3 interaction is crucial for hepatocyte growth factor dependent decrease of CXCR4 expression in highly invasive breast tumor cells. Mol Cancer Res 5(8):833–845. doi:10.1158/1541-7786.MCR-07-0054

    Article  PubMed  CAS  Google Scholar 

  71. Rahimi N, Hung W, Tremblay E, Saulnier R, Elliott B (1998) c-Src kinase activity is required for hepatocyte growth factor-induced motility and anchorage-independent growth of mammary carcinoma cells. J Biol Chem 273(50):33714–33721

    Article  PubMed  CAS  Google Scholar 

  72. Duval M, Le Boeuf F, Huot J, Gratton JP (2007) Src-mediated phosphorylation of Hsp90 in response to vascular endothelial growth factor (VEGF) is required for VEGF receptor-2 signaling to endothelial NO synthase. Mol Biol Cell 18(11):4659–4668. doi:10.1091/mbc.E07-05-0467

    Article  PubMed  CAS  Google Scholar 

  73. Eliceiri BP, Puente XS, Hood JD, Stupack DG, Schlaepfer DD, Huang XZ, Sheppard D, Cheresh DA (2002) Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling. J Cell Biol 157(1):149–160. doi:10.1083/jcb.200109079

    Article  PubMed  CAS  Google Scholar 

  74. Lesslie DP, Summy JM, Parikh NU, Fan F, Trevino JG, Sawyer TK, Metcalf CA, Shakespeare WC, Hicklin DJ, Ellis LM, Gallick GE (2006) Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases. Br J Cancer 94(11):1710–1717. doi:10.1038/sj.bjc.6603143

    PubMed  CAS  Google Scholar 

  75. Guy CT, Muthuswamy SK, Cardiff RD, Soriano P, Muller WJ (1994) Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. Genes Dev 8(1):23–32

    Article  PubMed  CAS  Google Scholar 

  76. Muthuswamy SK, Muller WJ (1994) Activation of the Src family of tyrosine kinases in mammary tumorigenesis. Adv Cancer Res 64:111–123

    Article  PubMed  CAS  Google Scholar 

  77. Muthuswamy SK, Siegel PM, Dankort DL, Webster MA, Muller WJ (1994) Mammary tumors expressing the neu proto-oncogene possess elevated c-Src tyrosine kinase activity. Mol Cell Biol 14(1):735–743

    PubMed  CAS  Google Scholar 

  78. Wilson GR, Cramer A, Welman A, Knox F, Swindell R, Kawakatsu H, Clarke RB, Dive C, Bundred NJ (2006) Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity. Br J Cancer 95(10):1410–1414. doi:10.1038/sj.bjc.6603444

    Article  PubMed  CAS  Google Scholar 

  79. Zou D, Yoon HS, Anjomshoaa A, Perez D, Fukuzawa R, Guilford P, Humar B (2009) Increased levels of active c-Src distinguish invasive from in situ lobular lesions. Breast Cancer Res 11 (4):R45. doi:10.1186/bcr2332

  80. Boyer B, Bourgeois Y, Poupon MF (2002) Src kinase contributes to the metastatic spread of carcinoma cells. Oncogene 21(15):2347–2356. doi:10.1038/sj.onc.1205298

    Article  PubMed  CAS  Google Scholar 

  81. Edwards J (2010) Src kinase inhibitors: an emerging therapeutic treatment option for prostate cancer. Expert Opin Investig Drugs 19(5):605–614. doi:10.1517/13543781003789388

    Article  PubMed  CAS  Google Scholar 

  82. Elsberger B, Stewart B, Tatarov O, Edwards J (2010) Is Src a viable target for treating solid tumours? Curr Cancer Drug Targets 10(7):683–694

    Article  PubMed  CAS  Google Scholar 

  83. Onishi T, Hayashi N, Theriault RL, Hortobagyi GN, Ueno NT (2010) Future directions of bone-targeted therapy for metastatic breast cancer. Nat Rev Clin Oncol 7(11):641–651. doi:10.1038/nrclinonc.2010.134

    Google Scholar 

  84. Eissa SA, Zaki SA, El-Maghraby SM, Kadry DY (2005) Importance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Natl Canc Inst 17(1):51–55

    PubMed  Google Scholar 

  85. Azenshtein E, Luboshits G, Shina S, Neumark E, Shahbazian D, Weil M, Wigler N, Keydar I, Ben-Baruch A (2002) The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity. Cancer Res 62(4):1093–1102

    PubMed  CAS  Google Scholar 

  86. Dimberg J, Hugander A, Wagsater D (2006) Protein expression of the chemokine, CCL28, in human colorectal cancer. Int J Oncol 28(2):315–319

    PubMed  CAS  Google Scholar 

  87. Kawai Y, Kaidoh M, Yokoyama Y, Sano K, Ohhashi T (2009) Chemokine CCL2 facilitates ICAM-1-mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes. Cancer Sci 100(3):419–428. doi:10.1111/j.1349-7006.2008.01064.x

    Article  PubMed  CAS  Google Scholar 

  88. Kroeze KL, Jurgens WJ, Doulabi BZ, van Milligen FJ, Scheper RJ, Gibbs S (2009) Chemokine-mediated migration of skin-derived stem cells: predominant role for CCL5/RANTES. J Invest Dermatol 129(6):1569–1581. doi:10.1038/jid.2008.405

    Article  PubMed  CAS  Google Scholar 

  89. Luboshits G, Shina S, Kaplan O, Engelberg S, Nass D, Lifshitz-Mercer B, Chaitchik S, Keydar I, Ben-Baruch A (1999) Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res 59(18):4681–4687

    PubMed  CAS  Google Scholar 

  90. Makinoshima H, Dezawa M (2009) Pancreatic cancer cells activate CCL5 expression in mesenchymal stromal cells through the insulin-like growth factor-I pathway. FEBS Lett 583(22):3697–3703. doi:10.1016/j.febslet.2009.10.061

    Article  PubMed  CAS  Google Scholar 

  91. Soria G, Yaal-Hahoshen N, Azenshtein E, Shina S, Leider-Trejo L, Ryvo L, Cohen-Hillel E, Shtabsky A, Ehrlich M, Meshel T, Keydar I, Ben-Baruch A (2008) Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: a basis for tumor-promoting interactions. Cytokine 44(1):191–200. doi:10.1016/j.cyto.2008.08.002

    Article  PubMed  CAS  Google Scholar 

  92. Wigler N, Shina S, Kaplan O, Luboshits G, Chaitchik S, Keydar I, Ben-Baruch A (2002) Breast carcinoma: a report on the potential usage of the CC chemokine RANTES as a marker for a progressive disease. Isr Med Assoc J 4(11):940–943

    PubMed  Google Scholar 

  93. Wu Y, Li YY, Matsushima K, Baba T, Mukaida N (2008) CCL3-CCR5 axis regulates intratumoral accumulation of leukocytes and fibroblasts and promotes angiogenesis in murine lung metastasis process. J Immunol 181(9):6384–6393

    PubMed  CAS  Google Scholar 

  94. Hoar FJ, Chaudhri S, Wadley MS, Stonelake PS (2003) Co-expression of vascular endothelial growth factor C (VEGF-C) and c-erbB2 in human breast carcinoma. Eur J Cancer 39(12):1698–1703

    Article  PubMed  CAS  Google Scholar 

  95. Linderholm B, Grankvist K, Wilking N, Johansson M, Tavelin B, Henriksson R (2000) Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment. J Clin Oncol 18(7):1423–1431

    PubMed  CAS  Google Scholar 

  96. Ryden L, Jirstrom K, Haglund M, Stal O, Ferno M (2010) Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up. Breast Cancer Res Treat 120 (2):491–498. doi:10.1007/s10549-010-0758-6

  97. Jedeszko C, Victor BC, Podgorski I, Sloane BF (2009) Fibroblast hepatocyte growth factor promotes invasion of human mammary ductal carcinoma in situ. Cancer Res 69(23):9148–9155. doi:10.1158/0008-5472.CAN-09-1043

    Article  PubMed  CAS  Google Scholar 

  98. Mine S, Fujisaki T, Kawahara C, Tabata T, Iida T, Yasuda M, Yoneda T, Tanaka Y (2003) Hepatocyte growth factor enhances adhesion of breast cancer cells to endothelial cells in vitro through up-regulation of CD44. Exp Cell Res 288(1):189–197

    Article  PubMed  CAS  Google Scholar 

  99. Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP (1995) Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 375(6532):577–581

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Lynn Feasel and the staff at the Rockyview General Hospital Clinical Orthopaedics Department for their assistance in obtaining and processing bone samples. They would also like to thank Elizabeth Kornaga for help with the statistical analysis. 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”.

Conflicts of interest

None of the authors have a conflict of interest.

Author information

Authors and Affiliations

  1. Departments of Oncology and Pathology and Laboratory Medicine, Faculty of Medicine, University of Calgary, 1331 29 St, NW, Calgary, AB, T2N 4N2, Canada

    Brant Pohorelic, R. Singh, S. Parkin, K. Koro, A.-D. Yang, C. Egan & A. Magliocco

Authors
  1. Brant Pohorelic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Parkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Koro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A.-D. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Egan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Magliocco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Egan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pohorelic, B., Singh, R., Parkin, S. et al. Role of Src in breast cancer cell migration and invasion in a breast cell/bone-derived cell microenvironment. Breast Cancer Res Treat 133, 201–214 (2012). https://doi.org/10.1007/s10549-011-1753-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-011-1753-2

Keywords

Search

Navigation