Growth Factor-Induced Cell Motility in Tumor Invasion

Authors

  • Alan Wells From the Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, USA (A. Wells, J. Kassis, J. Solava), Department of Pathology, University of Alabama at Birmingham, USA (J. Kassis), Carver Research Institute, Tuskegee University, Tuskegee, AL, USA (T. Turner), Division of Bioengineering & Environmental Health and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA (D.A. Lauffenburger)
  • Jareer Kassis From the Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, USA (A. Wells, J. Kassis, J. Solava), Department of Pathology, University of Alabama at Birmingham, USA (J. Kassis), Carver Research Institute, Tuskegee University, Tuskegee, AL, USA (T. Turner), Division of Bioengineering & Environmental Health and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA (D.A. Lauffenburger)
  • James Solava From the Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, USA (A. Wells, J. Kassis, J. Solava), Department of Pathology, University of Alabama at Birmingham, USA (J. Kassis), Carver Research Institute, Tuskegee University, Tuskegee, AL, USA (T. Turner), Division of Bioengineering & Environmental Health and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA (D.A. Lauffenburger)
  • James Solava From the Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, USA (A. Wells, J. Kassis, J. Solava), Department of Pathology, University of Alabama at Birmingham, USA (J. Kassis), Carver Research Institute, Tuskegee University, Tuskegee, AL, USA (T. Turner), Division of Bioengineering & Environmental Health and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA (D.A. Lauffenburger)
  • Timothy Turner From the Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, USA (A. Wells, J. Kassis, J. Solava), Department of Pathology, University of Alabama at Birmingham, USA (J. Kassis), Carver Research Institute, Tuskegee University, Tuskegee, AL, USA (T. Turner), Division of Bioengineering & Environmental Health and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA (D.A. Lauffenburger)
  • Douglas A. Lauffenburger From the Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, USA (A. Wells, J. Kassis, J. Solava), Department of Pathology, University of Alabama at Birmingham, USA (J. Kassis), Carver Research Institute, Tuskegee University, Tuskegee, AL, USA (T. Turner), Division of Bioengineering & Environmental Health and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA (D.A. Lauffenburger)

DOI:

https://doi.org/10.1080/028418602753669481

Abstract

Tumor progression to the invasive and metastatic states dramatically enhances the morbidity and mortality of cancer. Rational therapeutic interventions will only be possible when we understand the molecular mechanisms governing the cell behavior underlying this transformation. For invasion, a subpopulation of tumor cells must recognize the extracellular matrix barrier, modify the barrier, migrate through the barrier, and then proliferate in the adjacent but ectopic locale. Prevention of any one of these steps would prevent invasion, but determining the most sensitively dysregulated step should provide the most promising therapeutic index. In many invasive tumors, upregulation of active motility is stimulated by growth factor receptor signaling, the EGF receptor being the most frequently implicated. Two key downstream molecular switches, PLC &#110 and m-calpain, are required for growth factor-induced motility but not basal, matrix-stimulated motility. Inhibition of either of these enzymes blocks in vitro and in vivo invasion of prostate, breast, and bladder carcinomas and glioblastomas. These represent novel and potentially selective targets for drug development. Future advances in the imaging of tumors in animals and ex vivo organ culture systems should provide additional new targets.

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Published

2002-01-01

How to Cite

Wells, A., Kassis, J., Solava, J., Solava, J., Turner, T., & Lauffenburger, D. A. (2002). Growth Factor-Induced Cell Motility in Tumor Invasion. Acta Oncologica, 41(2), 124–130. https://doi.org/10.1080/028418602753669481

Issue

Vol. 41 No. 2 (2002): Acta Oncologica

Section

Articles