This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, X. Articles by McKeehan, W. L. Search for Related Content PubMed PubMed Citation Articles by Wu, X. Articles by McKeehan, W. L.

A Rare Premalignant Prostate Tumor Epithelial Cell Syndecan-1 Forms a Fibroblast Growth Factor-binding Complex with Progression-promoting Ectopic Fibroblast Growth Factor Receptor 1¹

Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030-3303 [X. W., M. K., F. W., C. J., C. Y., W. L. M.]; Graduate School of Biomedical Sciences, The University of Texas-Houston Health Science Center, Houston, Texas 77030 [X. W., C. Y.]; and Central Research Laboratories, Zeria Pharmaceutical Company, Limited, Kohnan-machi, Ohsato-Gun, Saitama 360-0111, Japan [M. K.]

The abnormal appearance and age-dependent loss of resident fibroblast growth factor receptor-2 (FGFR2) and gain of activity of FGFR1 in epithelial cells is a hallmark of the slow progression to malignancy in some models of prostate cancer. Pericellular matrix heparan sulfate (HS) is an integral subunit of the FGFR tyrosine kinase complex that restricts activity in absence of FGF, facilitates binding of an activating FGF, and confers specificity for FGF isoforms. In this report, we isolated and purified HS proteoglycan (HSPG) from premalignant prostate tumor epithelial cells based on the ability of the HS chains to form a binary complex with immunoglobulin module II of the ectopic and progression-promoting FGFR1 that was competent to bind FGF. The FGFR1 affinity-purified product exhibited a specific activity of over 600 times that of crude cellular HSPG enriched from cell lysates by ion exchange chromatography. The purified preparation exhibited a single NH₂-terminal sequence with 11 of 13 residues identical to syndecan-1. The activity of purified recombinant glutathione S-transferase-tagged syndecan-1 expressed in premalignant epithelial cells confirmed that syndecan-1 bears HS chains that exhibit the rare motif that forms the FGF-binding complex with ectopic FGFR1. These results are the first to identify by affinity purification a specific HSPG core protein, the HS chains of which act as an integral subunit of the FGFR complex. The results suggest that syndecan-1 provides HS chains in premalignant epithelial cells to both the FGFR2- and FGFR1-signaling complexes that are integral to their dual roles in progression to malignancy.

This article has been cited by other articles:

				M. Mimeault and S. K. Batra Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies Carcinogenesis, January 1, 2006; 27(1): 1 - 22. [Abstract] [Full Text] [PDF]

				C. Jin, F. Wang, X. Wu, C. Yu, Y. Luo, and W. L. McKeehan Directionally Specific Paracrine Communication Mediated by Epithelial FGF9 to Stromal FGFR3 in Two-Compartment Premalignant Prostate Tumors Cancer Res., July 1, 2004; 64(13): 4555 - 4562. [Abstract] [Full Text] [PDF]

				C. Jin, K. McKeehan, W. Guo, S. Jauma, M. M. Ittmann, B. Foster, N. M. Greenberg, W. L. McKeehan, and F. Wang Cooperation between Ectopic FGFR1 and Depression of FGFR2 in Induction of Prostatic Intraepithelial Neoplasia in the Mouse Prostate Cancer Res., December 15, 2003; 63(24): 8784 - 8790. [Abstract] [Full Text] [PDF]

				X. Wu, C. Jin, F. Wang, C. Yu, and W. L. McKeehan Stromal Cell Heterogeneity in Fibroblast Growth Factor-mediated Stromal-Epithelial Cell Cross-Talk in Premalignant Prostate Tumors Cancer Res., August 15, 2003; 63(16): 4936 - 4944. [Abstract] [Full Text] [PDF]

				D. Qiao, K. Meyer, C. Mundhenke, S. A. Drew, and A. Friedl Heparan Sulfate Proteoglycans as Regulators of Fibroblast Growth Factor-2 Signaling in Brain Endothelial Cells. SPECIFIC ROLE FOR GLYPICAN-1 IN GLIOMA ANGIOGENESIS J. Biol. Chem., April 25, 2003; 278(18): 16045 - 16053. [Abstract] [Full Text] [PDF]

				S. Knox, C. Merry, S. Stringer, J. Melrose, and J. Whitelock Not All Perlecans Are Created Equal. INTERACTIONS WITH FIBROBLAST GROWTH FACTOR (FGF) 2 AND FGF RECEPTORS J. Biol. Chem., April 19, 2002; 277(17): 14657 - 14665. [Abstract] [Full Text] [PDF]

				F. Wang, K. McKeehan, C. Yu, and W. L. McKeehan Fibroblast Growth Factor Receptor 1 Phosphotyrosine 766: Molecular Target for Prevention of Progression of Prostate Tumors to Malignancy Cancer Res., March 1, 2002; 62(6): 1898 - 1903. [Abstract] [Full Text] [PDF]