© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 19, 1663-1669,
October 6, 1999
© 1999 Oxford University Press
Growth Regulation of Prostatic Stromal Cells by Prostate-Specific Antigen
Affiliations of authors: D. M. Sutkowski, R. L. Goode, C. Teater, A. M. McNulty, H. M. Hsiung, G. W. Becker, B. L. Neubauer, Lilly Research Laboratories, a Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN; J. Baniel, Department of Urology, Indiana University School of Medicine, Indianapolis; P. Cohen, Division of Pediatric Endocrinology, Children's Hospital of Philadelphia, PA.
Correspondence to: Blake Lee Neubauer, Ph.D., Cancer Research 0546, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
BACKGROUND: Prostate-specific antigen (PSA) is a serine protease that can cleave insulin-like growth factor-binding protein-3 (IGFBP3), thereby decreasing its affinity for insulin-like growth factor-I (IGF-I). Dissociation of the IGF-I-IGFBP3 complex renders IGF-I available to bind to its receptor and stimulates cellular proliferation. We evaluated the potential for PSA to modulate the effects of IGF-I and IGFBP3 on the proliferation of human benign prostatic hyperplasia (BPH)-derived fibromuscular stromal cells in primary cultures. METHODS: We cultured BPH-derived stromal cells for 48 hours in serum-free RPMI-1640 medium supplemented with 0.2% bovine serum albumin and studied the effects of IGF-I, IGFBP3, PSA, and ZnCl2 at varying concentrations. Differences in cell growth between control and treated cultures were evaluated by use of Dunnett's test. Concentration-related trends were evaluated by linear regression of log-transformed concentrations of test reagents on BPH-derived stromal cell number responses. Statistical tests were two-sided. RESULTS: We observed a concentration-dependent proliferative response of BPH-derived stromal cells to IGF-I. IGFBP3 inhibited this response in a concentration-dependent fashion. IGFBP3 alone had no effect on stromal cell proliferation. When stromal cells were incubated with PSA alone or with PSA, IGF-I, and IGFBP3, an increase in stromal cell numbers that was dependent on PSA concentration was evident in both instances. Zinc, an endogenous inhibitor of PSA enzymatic activity, was able to attenuate the stimulatory effect of PSA at intraprostatic physiologic concentrations. CONCLUSIONS: These results are consistent with the idea that PSA can modulate in vitro interactions between IGF-I and IGFBP3 and suggest that PSA may play a role in the regulation of human prostatic fibromuscular cell growth.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Patane and F. Marte Prostate-specific antigen kallikrein: from prostate cancer to cardiovascular system Eur. Heart J., May 2, 2009; 30(10): 1169 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Niu, S. Yeh, H. Miyamoto, G. Li, S. Altuwaijri, J. Yuan, R. Han, T. Ma, H.-C. Kuo, and C. Chang Tissue Prostate-Specific Antigen Facilitates Refractory Prostate Tumor Progression via Enhancing ARA70-Regulated Androgen Receptor Transactivation Cancer Res., September 1, 2008; 68(17): 7110 - 7119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Serrano, L. Baglietto, H. Johansson, F. Mariette, R. Torrisi, M. Onetto, M. Paganuzzi, and A. Decensi Effect of the Synthetic Retinoid Fenretinide on Circulating Free Prostate-Specific Antigen, Insulin-Like Growth Factor-I, and Insulin-Like Growth Factor Binding Protein-3 Levels in Men with Superficial Bladder Cancer Clin. Cancer Res., March 1, 2005; 11(5): 2083 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Borgono, I. P. Michael, and E. P. Diamandis Human Tissue Kallikreins: Physiologic Roles and Applications in Cancer Mol. Cancer Res., May 1, 2004; 2(5): 257 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. O. Roberts, D. J. Jacobson, C. J. Girman, T. Rhodes, G. G. Klee, M. M. Lieber, and S. J. Jacobsen Insulin-like Growth Factor I, Insulin-like Growth Factor Binding Protein 3, and Urologic Measures of Benign Prostatic Hyperplasia Am. J. Epidemiol., May 1, 2003; 157(9): 784 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Niemela, J. Lovgren, M. Karp, H. Lilja, and K. Pettersson Sensitive and Specific Enzymatic Assay for the Determination of Precursor Forms of Prostate-specific Antigen after an Activation Step Clin. Chem., August 1, 2002; 48(8): 1257 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Untergasser, H. Rumpold, E. Plas, M. Witkowski, and P. Berger Seminal Plasma Factors Induce in Vitro PRL Secretion in Smooth Muscle Cells of the Human Prostate J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5577 - 5584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Taplin and S.-M. Ho The Endocrinology of Prostate Cancer J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3467 - 3477. [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Yousef and E. P. Diamandis The New Human Tissue Kallikrein Gene Family: Structure, Function, and Association to Disease Endocr. Rev., April 1, 2001; 22(2): 184 - 204. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. C. Dixon, K. B. Knopf, and W. D. Figg The Control of Prostate-Specific Antigen Expression and Gene Regulation by Pharmacological Agents Pharmacol. Rev., March 1, 2001; 53(1): 73 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. H. Afar, I. Vivanco, R. S. Hubert, J. Kuo, E. Chen, D. C. Saffran, A. B. Raitano, and A. Jakobovits Catalytic Cleavage of the Androgen-regulated TMPRSS2 Protease Results in Its Secretion by Prostate and Prostate Cancer Epithelia Cancer Res., February 1, 2001; 61(4): 1686 - 1692. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. P. Connell, L. Ignacio, D. Haraf, A. M. Awan, H. Halpern, I. Abdalla, J. Nautiyal, A. B. Jani, R. R. Weichselbaum, and S. Vijayakumar Equivalent Racial Outcome After Conformal Radiotherapy for Prostate Cancer: A Single Departmental Experience J. Clin. Oncol., January 1, 2001; 19(1): 54 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Finne, A. Auvinen, H. Koistinen, W.-M. Zhang, L. Määttänen, S. Rannikko, T. Tammela, M. Seppälä, M. Hakama, and U.-H. Stenman Insulin-Like Growth Factor I Is Not a Useful Marker of Prostate Cancer in Men with Elevated Levels of Prostate-Specific Antigen J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2744 - 2747. [Abstract] [Full Text]
|
|
|
|
|
|
E. P. Diamandis Prostate-specific Antigen: A Cancer Fighter and a Valuable Messenger? Clin. Chem., July 1, 2000; 46(7): 896 - 900. [Abstract] [Full Text] [PDF]
|
|