Co-inoculation of tumorigenic rat prostate mesenchymal cells with non-tumorigenic epithelial cells results in the development of carcinosarcoma in syngeneic and athymic animals

Authors

  • Leland W. K. Chung,

    Corresponding author
    1. Departments of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    • Departments of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Search for more papers by this author
  • Shi-Ming Chang,

    1. Departments of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Search for more papers by this author
  • Carol Bell,

    1. Departments of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Current affiliation:
    1. Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309
    Search for more papers by this author
  • Haiyen E. Zhau,

    1. Departments of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Search for more papers by this author
  • Jae Y. Ro,

    1. Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Search for more papers by this author
  • Andrew C. Von Eschenbach

    1. Departments of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Search for more papers by this author

Abstract

Co-inoculation of NbF-I and NbE-I s.c. into either adult male syngeneic rats or athymic nude mice induced the development of tumors that resembled carcinosarcoma on histopathologic evaluation. These tumors were composed of a mixture of adenocarcinoma and fibrosarcoma and were induced by the mixtures of NbF-I and NbE-I cells at a ratio ranging from 0.001 to 3.2; inoculation of NbF-I alone resulted in the development of fibrosarcoma. Flow-cytometric analysis showed that the epithelial cells subcloned from the carcinosarcoma had a DNA profile like that of their parental cell line and remained non-tumorigenic. When co-inoculated with the tumorigenic fibroblasts in syngeneic hosts, however, the subcloned epithelial cells again formed carcinosarcomas. Our results indicate that cell fusion between epithelial cells and fibroblasts is an unlikely explanation for tumorigenicity. We propose that prostatic fibroblasts exert a directive influence on their adjacent epithelial cells through a paracrine mechanism that determines epithelial growth and tumorigenicity in vivo.

Ancillary