EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells

Timothy Turner, Philip Chen, Lyndon J. Goodly, Alan Wells

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Carcinomas of the prostate and other lineages often present an autocrine stimulatory loop acting via the EGF receptor (EGFR). We have recently shown that EGFR-mediated signals enhance DU-145 prostate carcinoma cell transmigration of an extracellular matrix in vitro, and that this increased invasiveness was independent of proteolytic degradation of the matrix (Xie et al., 1995, Clin Exp Metastasis, 13, 407). To determine whether up-regulated EGFR signaling promotes tumor progression in vivo and to define the EGFR-induced cell property responsible, we inoculated athymic mice with genetically-engineered DU-145 cells. Parental DU-145 cells and those transduced to overexpress a full-length wild type (WT) EGFR formed tumors and metastasized to the lung when inoculated in the prostate and peritoneal cavity. The WT DU-145 tumors were more invasive. DU-145 cells expressing a mitogenically-active, but motility-deficient (c'973) EGFR formed small, non-invasive tumors without evidence of metastasis. All three sublines demonstrated identical, EGFR-dependent rates of cell growth in vitro, suggesting that the differential invasiveness was not due to altered growth rates. To determine whether cell motility may be, in part, responsible for tumor invasiveness, we treated WT DU-145 intraperitoneal tumors with a pharmacologic agent (U73122) which blocks EGFR-mediated cell motility but not mitogenesis. Under this treatment regimen, the WT DU-145 cells formed tumors of similar numbers and size to those formed without treatment; however, these tumors were much less invasive. These data suggest that EGFR-mediated cell motility is an important mechanism involved in tumor progression, and that this cell property may represent a novel target to limit the spread of tumors.

Original languageEnglish
Pages (from-to)409-418
Number of pages10
JournalClinical and Experimental Metastasis
Volume14
Issue number4
DOIs
StatePublished - Nov 11 1996

Fingerprint

Epidermal Growth Factor Receptor
Prostate
Carcinoma
Neoplasms
Cell Movement
Neoplasm Metastasis
Peritoneal Cavity
Growth
Nude Mice
Extracellular Matrix
Lung

Keywords

  • Epidermal growth factor receptor
  • Phospholipase C
  • Tumor progression

ASJC Scopus subject areas

  • Cancer Research

Cite this

EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells. / Turner, Timothy; Chen, Philip; Goodly, Lyndon J.; Wells, Alan.

In: Clinical and Experimental Metastasis, Vol. 14, No. 4, 11.11.1996, p. 409-418.

Research output: Contribution to journalArticle

Turner, Timothy ; Chen, Philip ; Goodly, Lyndon J. ; Wells, Alan. / EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells. In: Clinical and Experimental Metastasis. 1996 ; Vol. 14, No. 4. pp. 409-418.
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