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United States Patent | 5,679,636 |
Chung , et al. | October 21, 1997 |
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.
Inventors: | Chung; Leland W. K. (Houston, TX), Chan; James C. (Sugarland, TX), Logothetis; Christopher J. (Houston, TX) |
Assignee: |
Board of Regents, The University of Texas
(Austin,
TX)
|
Appl. No.: | 08/341,297 |
Filed: | November 15, 1994 |
Application Number | Filing Date | Patent Number | Issue Date | ||
859228 | Mar., 1992 | ||||
Current U.S. Class: | 514/9.1 ; 514/19.5; 514/19.8; 514/9.5; 530/350; 530/399; 530/412; 530/413 |
Current International Class: | C07K 14/435 (20060101); C07K 16/22 (20060101); C07K 14/475 (20060101); C07K 14/51 (20060101); C07K 16/18 (20060101); A61K 38/00 (20060101); A61K 038/18 (); C07K 014/475 (); A23J 001/00 () |
Field of Search: | 514/2 530/350,399,412,413 |
M Chackal-Roy and B.R. Zetter, Faseb Journal, 4(7) :A1989, 1990, Abstract No. 1723. . M. Chackal-Roy et al., "Stimulation of Human Prostatic Carcinoma Cell Growth by Factors Present in Human Bone Marrow," The American Society for Clinical Investigation, Inc., 84:43-50, 1989. . Leland W.K. Chung, "Fibroblasts Are Critical Determinants in Prostatic Cancer Growth and Dissemination," Cancer and Metastasis Reviews, 10:263-274, 1991. . Leland, W.K. Chung et al., "Reciprocal Mesenchymal-Epithelial Interaction Affecting Prostate Tumor Growth an Hormonal Responsiveness," Cancer Surveys, 11:91-121, 1991. . Martin Gleave et al., "Acceleration of Human Prostate Cancer Growth in Vivo by Factors Produced by Prostate and Bone Fibroblasts," Cancer Research, 51:3753-3761, 1991. . Martin Gleave et al., Journal of Urology, 145(4 Suppl.), 213A, 1991, Abstract No. 1. . M.E. Gleave et al., "Prostate and Bone Fibroblasts Induce Human Prostate Cancer Growth in Vivo: Implications for Bidirectional Tumor-Stromal Cell Interaction in Prostate Carcinoma Growth and Metastasis," Journal of Urology, 147:1151-1159, 1992. . Martin E. Gleave et al., "Serum Prostate Specific Antigen Levels in Mice Bearing Human Prostate LNCaP Tumors Are Determined by Tumor Volume and Endocrine and Growth Factors," Cancer Research, 52:1598-1605, 1992. . Zetter, Bruce R. et al., "Selective Stimulation of Prostatic Carcinoma Cell Proliferation by Transferrin," Proceedings of the National Academy of Science, 89:6197-6201, 1992. . Dialog Search Report, 1992.. |
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