Acceleration of Human Prostate Cancer Growth in Vivoby Factors Produced by Prostate and Bone Fibroblasts

Martin Gleave, Jer Tsong Hsieh, Chuan Gao, Andrew C. Von Eschenbach, Leland W K Chung

Research output: Contribution to journalArticle

391 Scopus citations

Abstract

Prostate cancer, the most prevalent cancer affecting men, frequently metastasizes to the axial skeleton where it produces osteoblastic lesions with growth rates often exceeding that of the primary tumor. To evaluate the role of tumor cell-host stromal interaction and stromal specific growth factors (GFs) in prostate cancer growth and progression, we coinoculated athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts s.c. LNCaP tumor formation was most con sistently induced by human bone (MS) fibroblasts (62%), followed by embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney, or human lung CCD16 fibroblasts. Carcinomas formed prefer entially in male hosts, demonstrating in vivo androgen sensitivity. The human prostate component of these tumors was confirmed with immunohistochemical staining for prostate-specific antigen (PSA), Northern analysis for PSA expression, and Southern analysis for human repetitive Alu sequences. Elevations in serum PSA paralleled the histomorphological and biochemical findings. LNCaP and fibroblast cell-conditioned media (CM) was used to deter mine whether autocrine and panierino mitogenic pathways exist between LNCaP and fibroblast cells in vitro, and various defined GFs were tested to identify possible active factors. Mitogenic assays revealed a 200-300% bidirectional stimulation between LNCaP and bone or prostate fibroblastderived CM. Lung, normal rat kidney, and 3T3 fibroblast CM were not mitogenic for LNCaP cells. Among the purified GFs tested basic fibro blast growth factor (bFGF) was the most potent mitogen, stimulating LNCaP growth 180% in a concentration-dependent manner. Transform ing growth factor a and epidermal growth factor were both minimally mitogenic. Coinoculation of LNCaP cells with a slowly adsorbed matrix (Gelfoam) adsorbed with bFGF or dialyzed and concentrated rUGM or MS CM was also capable of inducing LNCaP tumor formation in vivo. These observations illustrate that fibroblasts differentially modulate prostate cancer growth through the release of paracrine-mediated GFs, possibly including bFGF, and that tumor-stromal cell interactions play an important role in prostate cancer growth and progression.

Original languageEnglish (US)
Pages (from-to)3753-3761
Number of pages9
JournalCancer research
Volume51
Issue number14
StatePublished - Jul 1991

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gleave, M., Hsieh, J. T., Gao, C., Von Eschenbach, A. C., & Chung, L. W. K. (1991). Acceleration of Human Prostate Cancer Growth in Vivoby Factors Produced by Prostate and Bone Fibroblasts. Cancer research, 51(14), 3753-3761.