Growth Factor-Induced Cell Motility in Tumor Invasion

• Published in: Acta oncologica Vol. 41; no. 2; pp. 124 - 130
• Main Authors: Wells, Alan, Kassis, Jareer, Solava, James, Turner, Timothy, Lauffenburger, Douglas A.
• Format: Journal Article
• Language: English
• Published: Basingstoke Informa UK Ltd 2002; Taylor & Francis
• Subjects: Animals; Biological and medical sciences; Cell Movement; Dissemination; ErbB Receptors - metabolism; Growth Substances - physiology; Humans; Medical sciences; Neoplasm Invasiveness; Neoplasms - metabolism; Neoplasms - pathology; Other treatments; Signal Transduction; Treatment. General aspects; Tumor cell; Tumors; Antineoplastic agent; Cell proliferation; Motility; Enzyme; Space occupying lesion; Cysteine endopeptidases; Enzyme inhibitor; Calpain; Malignant tumor; Experimental study; In vitro; Cell substratum interaction; Peptidases; In vivo; Epidermal growth factor; Enzymatic activity; Hydrolases; Extracellular matrix; Physiology; Medical application; Tumor cell; Growth factor
• ISSN: 0284-186X; 1651-226X
• DOI: 10.1080/028418602753669481

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.