European Journal of Cancer
Volume 39, Issue 13 , Pages 1927-1935 , September 2003

Pyrrolopyrimidine c-Src inhibitors reduce growth, adhesion, motility and invasion of prostate cancer cells in vitro

  • I. Recchia

      Affiliations

    • Department of Experimental Medicine, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy
  • ,
  • N. Rucci

      Affiliations

    • Department of Experimental Medicine, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy
  • ,
  • C. Festuccia

      Affiliations

    • Department of Experimental Medicine, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy
  • ,
  • M. Bologna

      Affiliations

    • Department of Basic and Applied Biology University of L'Aquila, L'Aquila, Italy
  • ,
  • A.R. MacKay

      Affiliations

    • Department of Experimental Medicine, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy
  • ,
  • S. Migliaccio

      Affiliations

    • Department of Experimental Medicine, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy
  • ,
  • M. Longo

      Affiliations

    • Department of Histology and Medical Embryology, University “La Sapienza”, Rome, Italy
  • ,
  • M. Šuša

      Affiliations

    • Novartis Pharma Research, Therapeutic Area Arthritis and Bone Metabolism, Basel, Switzerland
  • ,
  • D. Fabbro

      Affiliations

    • Novartis Pharma Research, Therapeutic Area Arthritis and Bone Metabolism, Basel, Switzerland
  • ,
  • A. Teti

      Affiliations

    • Department of Experimental Medicine, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39-0862-433511; fax: +39-0862-433523

Received 13 September 2002 ,Revised 6 February 2003 ,Accepted 13 February 2003.

References 

  1. Abi-Aad AS, Opsomer RJ. Prostate cancer-treatment of disseminated disease. Acta Urol. Belg. 1995;64:67–76
  2. Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nature Rev. Cancer. 2001;1:34–45
  3. Hellawell GO, Brewster SF. Growth factors and their receptors in prostate cancer. BJU Int. 2002;89:230–240
  4. Frame MC. Src in cancer (deregulation and consequences for cell behaviour). Biochim. Biophys. Acta. 2002;160:114–130
  5. Lee L-F, Guan J, Qiu Y, Kung H-J. Neuropeptide-induced androgen independence in prostate cancer cells (roles of nonreceptor tyrosine kinase Etk/Bmx, Src, and focal adhesion kinase). Mol. Cell Biol. 2001;21:8385–8397
  6. Šuša M, Teti A. Tyrosine kinase Src inhibitors (potential therapeutic applications). Drug News Perspect. 2000;13:169–175
  7. Sawyer T, Boyce B, Dalgarno D, Iuliucci J. Src inhibitors (genomics to therapeutics). Expert Opin Investig Drugs. 2001;10:1327–1344
  8. Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu. Rev. Cell. Dev. Biol. 1997;13:513–609
  9. Missbach M, Jeschke M, Feyen J, Muller K, et al.  A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone. 1999;24:437–449
  10. Missbach M, Altmann E, Widler L, et al.  Substituted 5,7-diphenyl-pyrrolo[2,3d]pyrimidines (potent inhibitors of the tyrosine kinase c-Src). Bioorg. Med. Chem. Lett. 2000;10:945–949
  11. Šuša M, Luong-Nguyen NH, Crespo J, Maier R, Missbach M, McMaster G. Active recombinant human tyrosine c-Yes (expression in baculovirus system, purification, comparison to c-Src, and inhibition by a c-Src inhibitor). Protein Expr. Purif. 2000;19:99–106
  12. Albini A, Iwamoto Y, Kleinman HK, et al.  A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987;47:3239–3245
  13. Robinson D, He F, Pretlow T, Kung H-J. A tyrosine kinase profile of prostate carcinoma. Proc. Natl. Acad. Sci. USA. 1996;93:5958–5962
  14. Ma YC, Huang XY. Novel regulation and function of Src tyrosine kinase. Cell Mol. Life Sci. 2002;59:456–462
  15. Abram CL, Courtneidge SA. Src family tyrosine kinases and growth factor signaling. Exp. Cell Res. 2000;254:1–13
  16. Alessandro R, Kohn EC. Signal transduction targets in invasion. Clin. Exp. Metastasis. 2002;19:265–273
  17. Martin KH, Slack JK, Boerner SA, Martin CC, Parsons JT. Integrin connections map (to infinity and beyond). Science. 2002;296:1652–1653
  18. Frisch SM, Screaton RA. Anoikis mechanisms. Curr. Opin. Cell. Biol. 2001;13:555–562
  19. Frame MC, Fincham VJ, Carragher NO, Wyke JA. v-Src's hold over actin and cell adhesions. Nat. Rev. Mol. Cell. Biol. 2002;3:233–245
  20. Slack JK, Adams RB, Rovin JD, Bissonette EA, Stoker CE, Parsons JT. Alterations in the focal adhesion kinase/Src signal transduction pathway correlates with increased migratory capacity of prostate carcinoma cells. Oncogene. 2001;20:1152–1163
  21. Sakamoto M, Takamura M, Ino Y, Miura A, Genda T, Hirohashi S. Involvement of c-Src in carcinoma cell motility and metastasis. Jpn. J. Cancer Res. 2001;92:941–946
  22. Sato H, Kita M, Seiki M. v-Src activates the expression of 92-kDa type IV collagenase gene through the AP-1 site and the GT box homologous to retinoblastoma control elements. A mechanism regulating gene expression independent of that by inflammatory cytokines. J. Biol. Chem. 1993;268:23458–23460
  23. Norikate H, Miyamori H, Goto C, Seiki M, Sato H. Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in metastatic MDCK cells transformed by v-src. Clin. Exp. Metastasis. 1999;17:105–110
  24. Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991;64:693–702
  25. Marzia M, Sims NA, Voit S, et al.  Decreased c-Src expression enhances osteoblast differentiation and bone formation. J. Cell. Biol. 2000;151:311–320
  26. Mundy GR. Mechanisms of bone metastasis. Cancer. 1997;80:1546–1556
  27. Yoneda T. Cellular and molecular basis of preferential metastasis of breast cancer to bone. J. Orthop. Sci. 2000;5:75–81
  28. Rubens RD. Bone metastases—the clinical problem. Eur. J. Cancer. 1998;34:210–213
  29. Clarke NW, McClure J, George NJ. Morphometric evidence for bone resorption and replacement in prostate cancer. Br. J. Urol. 1991;68:74–80
  30. Ikeda I, Miura T, Kondo I. Pyridinium cross-links as urinary markers of bone metastases in patients with prostate cancer. Br. J. Urol. 1996;77:102–106
  31. Šuša M, Glatt M, Teti A. Tumor bone diseases (molecular mechanisms and opportunities for novel treatment). Curr. Med. Chem. Anti Cancer Agents. 2001;1:319–329

PII: S0959-8049(03)00394-0

doi: 10.1016/S0959-8049(03)00394-0

European Journal of Cancer
Volume 39, Issue 13 , Pages 1927-1935 , September 2003