Bone and prostate-derived protein factors affecting prostate cancer growth, differentiation, and metastasis

摘要

The role of tumor cell-host stromal interaction and stromal- specific growth factors in prostate cancer growth, progression and metastasis to the axial skeleton were investigated. Following co- inoculation of athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts, human prostate-like tumor formation was consistently induced by human bone (MS) fibroblasts (62%), embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney (NRK), or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. A novel in vivo method in which a slowly adsorbed matrix (Gelfoam) was employed to deliver concentrated prostate and bone fibroblast-derived conditioned media was also found to induce LNCaP tumor formation in vivo. Such in vivo growth- promoting effects correlated with in vitro tests employing a soft agar colony-forming assay using rat prostate epithelial (NbE-1) cells as targets. A substantially purified human growth factor preparation is shown to contain distinct polypeptides with apparent M.sub.r s on SDS/PAGE of 227, 223, 218, 157, 90, 80, 48, and 20 kD, and to be distinct from bFGF. The human growth factor polypeptide of 157 kD was identified, in human bone marrow aspirates, by immunoblotting with the mAb MS 329.