Bone and prostate-derived protein factors affecting prostate cancer growth, differentiation, and metastasis
US5679636A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Nov 15, 1994 |
| Grant date | Oct 21, 1997 |
| Priority date | — |
| Expiry date | Nov 15, 2014 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K38/00
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
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,…
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