Differentiation and stromal-induced growth promotion of murine prostatic tumors

Prostate. 2002 May 15;51(3):175-88. doi: 10.1002/pros.10075.

Abstract

Background: We have derived a panel of p53-null prostatic "basal" and "luminal" epithelial cell lines and their ras transformed counterparts to study stromal/epithelial interactions and the properties of tumors arising from "basal" and "luminal" cells.

Methods: Previously derived normal murine prostatic "basal" epithelial (PE-B-1) and "luminal" epithelial (PE-L-1) cell lines were transformed with N-Ras. These lines and a spontaneously transformed "luminal" cell line were inoculated subcutaneously or orthotopically into athymic mice, alone or in combination with normal prostatic smooth muscle cells (SMC).

Results: All transformed lines formed subcutaneous tumors. SMC significantly enhanced the growth rate of the tumors arising from the "basal" and one of the "luminal" cell lines. The transformed "basal" line gave rise to tumors expressing both "basal" and "luminal" cytokeratins.

Conclusions: Prostatic SMC promote the growth of transformed epithelial cells, suggesting that prostatic stroma may promote tumor development. Furthermore, transformed "basal" cells give rise to tumors containing "luminal" cells, suggesting that although most human tumors have a "luminal" phenotype, they may originate from transformed "basal" cells.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agar
  • Animals
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cell Line, Transformed
  • Cell Transplantation
  • Culture Media
  • Dihydrotestosterone / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth / cytology
  • Neoplasm Transplantation
  • Phenotype
  • Prostate / cytology
  • Prostate / physiology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Stromal Cells / physiology*
  • Stromal Cells / transplantation
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology
  • Tumor Cells, Cultured

Substances

  • Culture Media
  • Transforming Growth Factor beta
  • Dihydrotestosterone
  • Agar