Skip to main content
SpringerLink
Log in

Signal transduction therapy: a new paradigm

  • Chapter
Book cover Ovarian Cancer 3

  • 95 Accesses

Abstract

The advent of molecular medicine has brought new approaches to the treatment, diagnosis and evaluation of malignant disease. The molecular medicine of cancer has gone from cytotoxic chemotherapy to immunotherapy and now has entered into gene therapy interventions. Through recent scientific advances, immunotherapy has been brought from the laboratory bench to the clinic in the form of biological response modification, treatment with directed antibodies and combinations of cytokines and activated lymphocytes primed against the tumor. The optimal use and outcome of these forms of immunotherapy for ovarian cancer are still under investigation. The explosion in knowledge of how specific genes are involved in the process of cancer growth and metastasis has led to the areas of transgenic animal experimentation and human gene therapy. The concept of gene therapy for general cancer treatment is in the early stages of investigation and specific applications to ovarian cancer have not yet been introduced clinically. The last new target to be identified is that of signal transduction.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Spiegel, A. (1988) G proteins in clinical medicine. Hosp. Pract. June 93–111.

    Google Scholar 

  2. Rink, T.J. (1990) Receptor-mediated calcium entry. FEBS Lett. 268, 381–5.

    Article  PubMed  CAS  Google Scholar 

  3. Bean, B.P. (1989) Classes of calcium channels in vertebrate cells.Ann. Rev. Physiol 51 367–84.

    Article  CAS  Google Scholar 

  4. Simon, M.I., Strathmann, M.P., and Gautam, N. (1991) Diversity of G proteins in signal transduction. Science 252 802–8.

    Article  PubMed  CAS  Google Scholar 

  5. Aaronson, S.A. (1991) Growth factors and cancer. Science 2541146–53.

    Article  PubMed  CAS  Google Scholar 

  6. Tanaabe, T., Tadeshima, H., Mikami, A. et al. (1987) Primary structure of the receptor for calcium-channel blockers from skeletal muscle. Nature 328 313–18.

    Article  Google Scholar 

  7. Zernig, G. (1990) Widening potiential for Ca2+ antagonists: non-L-type Ca2+ channel interaction. TiPS 11 38–44.

    PubMed  CAS  Google Scholar 

  8. Kim, D., Lewis, D.L., Graziafei, L. et al (1989) G-protein βγ-subunits activate the cardiac muscarinic K+-channel via phospholipase A2. Nature 337 557–60.

    Article  CAS  Google Scholar 

  9. Brooks, R.C., McCarthy, K.D., Lapetina, E.G. and Morell, P. (1989) Receptor-stimulated phospholipase A2 activation is coupled to influx of external calcium and not to mobilization of intracellular calcium in C62B glioma cells, J.Biol Chem. 264 20147–53.

    PubMed  CAS  Google Scholar 

  10. Felder, C.C., Dieter, P., Kinsella, J. et al (1990) A transfected m5 muscarinic acetylcholine receptor stimulates phospholipse A2 by inducing both calcium influx and activation of protein kinase C. J. Pharm. Exp. Ther. 255 1140–7.

    CAS  Google Scholar 

  11. Marks, P.W., and Maxfield, F.R. (1990) Transient increases in cytosolic free calcium appear to be required for the migration of adherent human neutrophils.J. Cell Biol 110 43–52.

    Article  PubMed  CAS  Google Scholar 

  12. Hamachi, T., Hirata, M. and Koga, T. (1986) Origin of intracellular calcium and quantitation of mobilizable calcium in neutrophils stimulated with chemotactic peptide. Biochem. Biophys. Acta 889136–48.

    Article  PubMed  CAS  Google Scholar 

  13. Gusovsky, P., Leuders, J.E., Kohn, E.G. and Felder, C.C. (1993) Muscarinic receptor-mediated tyrosine phosphorylation of phospholipase C-gamma: alternative mechanism for cholinergic receptor-induced phosphoinosi-tide breakdown, J. Biol Chem. 268 7768–72.

    PubMed  CAS  Google Scholar 

  14. Bianchini, L., Todderud, G. and Grinstein, S. (1993) Cytosolic [Ca2+] homeostasis and tyrosine phosphorylation of phospholipase Cgamma2 in HL60 granulocytes. J. Biol Chem. 268, 3357–63.

    PubMed  CAS  Google Scholar 

  15. Tanaguchi, T., Kitagawea, H., Yasue, S. et al (1993) Protein-tyrosine kinase P72syk is activated by thrombin and is negatively regulated through Ca2+ regulation in platelets, J. Biol Chem. 268, 2277–9.

    Google Scholar 

  16. Guirguis, R., Margulies, I., Taraboletti, G. et al (1987) Cytokine-induced pseudopodial protrusion is coupled to tumor cell migration. Nature 329 261–3.

    Article  PubMed  CAS  Google Scholar 

  17. Kohn, E.G., Francis, E.A., Liotta, L.A. and Schiffmann, E. (1990) Heterogeneity of the motility responses in malignant tumor cells: a biological basis for the diversity and homing of metastatic cells. Int.J. Cancer 46287–92.

    Article  PubMed  CAS  Google Scholar 

  18. Aznavoorian, S.A., Stracke, M.L., Krutzsch, H. et al (1990) Signal transduction for Chemotaxis and haptotaxis by matrix molecules in tumor cells. J. Cell Biol 1101427–38.

    Article  PubMed  CAS  Google Scholar 

  19. Bar-Sagi, D. and Feramisco, J.R. (1986) Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by ras proteins. Science 2331061–8.

    Article  PubMed  CAS  Google Scholar 

  20. Brown, P.D., Levy, A.T., Margulies, I.M.K. et al (1990) Independent expression and cellular processing of Mr 72,000 type IV collage-nase and interstitial collagenase in human tumorigenic cell lines. Cancer Res. 50 6184–91.

    PubMed  CAS  Google Scholar 

  21. Ojcius, D.M., Zychlinsky, A., Zheng, L.M. and Young, J.D.E. (1991) lonophore-induced apop-tosis: role of DNA fragmentation and calcium fluxes. Exp. Cell Res. 19743–9.

    Article  PubMed  CAS  Google Scholar 

  22. Klee, C.B. (1988) Ca2+-dependent phospholipid (and membrane-) binding proteins. Biochemistry 27 6645–53.

    Article  PubMed  CAS  Google Scholar 

  23. Kojima, I., Matsunaga, H., Kurokawa, K. et al (1988)Calcium influx: an intracellular message of the mitogenic action of insulin-like growth factor-I. J.Biol Chem. 26316561–7.

    PubMed  CAS  Google Scholar 

  24. Kadowski, T., Koyasu, S., Nishida, E. et al (1987) Tyrosine phosphorylation of common and specific sets of cellular proteins rapidly induced by insulin, insulin-like growth factor I, and epidermal growth factor in an intact cell. J. Biol Chem. 262, 7342–50.

    Google Scholar 

  25. Nishibe, S., Wahl, M.I., Hernandez-Sotomayor, S.M.T.et al (1990) Increase of the catalytic activity of phospholipase C-yl by tyrosine phosphorylation.Science 2501253–6.

    Article  PubMed  CAS  Google Scholar 

  26. Kim, H.K., Kim, J.W., Zilberstein, A. et al (1991) PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gammal phosphorylation on tyrosine residues 783 and 1254. Cell 65435–41.

    Article  PubMed  CAS  Google Scholar 

  27. Wahl, M.I., Nishibe, S., Suh, P.G. et al (1989) Epidermal growth factor stimulates tyrosine phosphorylation of phospholipase C-II independently of receptor internalization and extracellular calcium.Proc. Natl Acad. Sci. USA 86,1568–72.

    Article  PubMed  CAS  Google Scholar 

  28. Kurachi, H., Morishige, K., Amemiya, K. et al (1991) Importance of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vivo. Cancer Res. 51, 5956–9.

    PubMed  CAS  Google Scholar 

  29. Blay, J. and Brown, K.D. (1985) Epidermal growth factor promotes chemotactic migration of cultured rat intestinal epithelial cells. J. Cell Physiol 124107–12.

    Article  PubMed  CAS  Google Scholar 

  30. Berchuck, A., Kamel, A., Whitaker, R. et al (1990) Overexpression of HER-2/ neu is associated with poor survival in advanced epithelial ovarian cancer.Cancer Res. 50,4087–91.

    PubMed  CAS  Google Scholar 

  31. Kornberg, L.J., Earp, H.S., Turner, C.E. et al (1991) Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of ßl integrins. Proc. Natl Acad. Sci. USA 88, 8392–6.

    Article  PubMed  CAS  Google Scholar 

  32. Hynes, R.O. (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 6911–25.

    Article  PubMed  CAS  Google Scholar 

  33. Savarese, D.M.F., Russel, J.T., Fatatis, A. and Liotta, L.A. (1992) Type IV collagen stimulates an increase in intracellular calcium: potential role in tumor cell motiUty. J. Biol Chem. 267 21928–35.

    PubMed  CAS  Google Scholar 

  34. McCarthy, J.B., Hagen, S.T. and Furcht, L.T. (1986) Human fibronectin contains distinct adhesion and motility-promoting domains for metastatic melanoma cells J. Cell Biol 102, 179–88.

    Article  PubMed  CAS  Google Scholar 

  35. Jaconi, M.E.E., Theler, J.M., Schlegel, W. et al (1991) Multiple elevations in cytosoHc-free Ca2+ in human neutrophils: initiation by adherence receptors of the integrin family. J. Cell Biol 112,1249–57.

    Article  PubMed  CAS  Google Scholar 

  36. Julius, D., Livelli, T.J., Jessell, T.M. and Axel, R. (1989) Ectopic expression of the serotonin Ic receptor and the triggering of malignant transformation. Science 2441057–62.

    Article  PubMed  CAS  Google Scholar 

  37. Allen, L.F., Lefkowitz, R.J., Caron, M.G. and Cotecchia, S. (1991) G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alphalB-adrenergic receptor enhances mitogenesis and tumori-genicity.Proc. Natl Acad. Sci. USA 88,11354–8.

    Article  PubMed  CAS  Google Scholar 

  38. Bonner, T.I. (1989) The molecular basis of muscarinic receptor diversity. TINS 12, 148–51.

    PubMed  CAS  Google Scholar 

  39. Felder, C.C., MacArthur, L., Ma A.L. et al (1993) Tumor-suppressor function of muscarinic acetylcholine receptors is associated with activation of receptor-operated calcium influx. Proc. Natl Acad. Sci USA 901706–10.

    Article  PubMed  CAS  Google Scholar 

  40. Gutkind, J.S., Novotny, E.A., Brann, M.R., and Robbins, K.C. (1991) Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes.Proc. Natl Acad. ScL USA 88,4703–7.

    Article  CAS  Google Scholar 

  41. Liotta, L.A. (1986) Tumor invasion and metastases-role of the extracellular matrix. Cancer Res. 46,1–7.

    Article  PubMed  CAS  Google Scholar 

  42. Furcht, L.T. (1986) Critical factors controUing angiogenesis: cell products, cell matrix, and growth factors. Lab. Invest. 55 505–9.

    PubMed  CAS  Google Scholar 

  43. Liotta, L.A., Steeg, P.S. and Stetler-Stevenson, W.G. (1991) Cancer metastasis and angiogenesis; an imbalance of positive and negative regulation. Cell 64, 327–36.

    Article  PubMed  CAS  Google Scholar 

  44. Tandon, A.K., Clark, G.M., Chamness, G.C. et al (1990) Cathepsin-D and prognosis in breast cancer. N. Engl J. Med. 322297–302.

    Article  PubMed  CAS  Google Scholar 

  45. Hollas, W., Blasi, F. and Boyd, D. (1991) Role of urokinase receptor in facilitating extracellular matrix invasion by cultured colon cancer. Cancer Res. 51 3690–5.

    PubMed  CAS  Google Scholar 

  46. Takeichi, M. (1991) Cadherin cell adhesion receptors as a morphogenetic regulator. Science 2511451–5.

    Article  PubMed  CAS  Google Scholar 

  47. Vleminck, K., Vakaet, L., Mareel, M. et al. (1991) Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.Cell 66107–19.

    Article  Google Scholar 

  48. Oka, H., Shiozaki, H., Kobayashi, K. et al (1993) Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and 57. its relationship to metastasis.Cancer Res. 53 1696–701.

    PubMed  CAS  Google Scholar 

  49. Shimoyama, Y., Nagafuchi, A., Fujita, S. et al.(1992) Cadherin dysfunction in a human cancer cell line: possible involvement of loss of 58. alpha-catenin expression in reduced cell-cell adhesiveness. Cancer Res. 52 5770–4.

    PubMed  CAS  Google Scholar 

  50. Stetler-Stevenson, W., Krutzsch, H.C., Wacher, M.P. et al. (1989) The activation of human type IV collagenase proenzyme, J.Biol. Chem. 264 59. 1353–6.

    PubMed  CAS  Google Scholar 

  51. Keski-Oja, J., Lohi, J., Tuuttila, A. et al. (1992) Proteolytic processing of the 72,000 Da type IV 60. collagenase by urokinase plasminogen activator. Exp. Cell. Res. 202 471–6.

    Article  PubMed  CAS  Google Scholar 

  52. Stossel, T.P. (1989) From signal to pseudopod. J. Biol. Chem. 26418261–4.

    PubMed  CAS  Google Scholar 

  53. Lester, B.R., McCarthy, J.B., Sun, Z. et al. (1989) G-protein involvement in matrix-mediated motility and invasion of high and low experimental metastatic B16 melanoma clones. Cancer Res. 49 5940–8.

    PubMed  CAS  Google Scholar 

  54. Liotta, L.A., Mandler, R., Murano, G. et al. (1986) Tumor cell autocrine motility factor. Proc. Natl Acad. Sci. USA 83 3302–6.

    Article  PubMed  CAS  Google Scholar 

  55. Stracke, M.L., Krutzsch, H.C., Unsworth, E.J. et al. (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J. Biol. Chem. 267 2524–9.

    PubMed  CAS  Google Scholar 

  56. Stracke, M.L., Guirguis, R., Liotta, L.A. and Schiffmann, E. (1987) Pertussis toxin inhibits stimulated motility independently of the adenylate cyclase pathway in human melanoma cells. Biochem. Biophys. Res. Commun. 146339–45.

    Article  PubMed  CAS  Google Scholar 

  57. Kohn, E.C., Liotta, L.A. and Schiffmann, E. (1990) Autocrine motility factor stimulates a three-fold increase in inositol trisphosphate in human melanoma cells. Biochem. Biophys. Res. Commun. 166 757–64.

    Article  PubMed  CAS  Google Scholar 

  58. Evans, C.P., Walsh, D.S., and Kohn, E.G. (1991) An autocrine motility factor secreted by the Dunning R-3327 rat prostatic adenocarcinoma cell subtype AT2.1. Int. J. Cancer 49 109–13.

    Article  PubMed  CAS  Google Scholar 

  59. Bochis, R., Ghabala, J.G. and Fisher, M.H. 5-amino or substituted amino 1,2,3-triazoles. US Patent 4,590,201, May 1986.

    Google Scholar 

  60. Kohn, E.G. and Liotta, L.A. (1990) L651582, anovel antiproliferative and antimetastasis agent. J. Natl Cancer Inst., 82 54–60.

    Article  PubMed  CAS  Google Scholar 

  61. Kohn, E.G., Sandeen, M.A. and Liotta, L.A. (1992) In vivo efficacy of a novel inhibitor of selected signal transduction pathways including calcium, arachidonate, and inositol phosphates. Cancer Res. 523208–12.

    PubMed  CAS  Google Scholar 

  62. Felder, G.G., Ma A.L., Liotta, L.A. and Kohn, E.G. (1991) The antiproliferative and anti-metastatic compound L6511582 inhibits muscarinic acetylcholine receptor-stimulated calcium influx and arachidonic acid release. J. Pharm. Exp. Ther. 257 967–71

    CAS  Google Scholar 

  63. Kohn, E.G., Felder, G.G., Jacobs, W. et al. (1994) Structure-function analysis of signal and growth inhibition by carboxyamido-triazole, GAL Cancer Res. 54 935–42.

    CAS  Google Scholar 

Download references

Authors
  1. E. C. Kohn
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynaecology, Northern General Hospital, Sheffield University, Sheffield, UK

    Frank Sharp  & Tony Blackett  & 

  2. The Samaritan Hospital for Women, St Mary’s Hospital Medical School, London, UK

    Peter Mason

  3. Division of Gynecologic Oncology, UCLA School of Medicine, Los Angeles, USA

    Jonathan Berek

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Chapman & Hall

About this chapter

Cite this chapter

Kohn, E.C. (1995). Signal transduction therapy: a new paradigm. In: Sharp, F., Mason, P., Blackett, T., Berek, J. (eds) Ovarian Cancer 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-0136-4_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-0136-4_26

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-0138-8

  • Online ISBN: 978-1-4757-0136-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation