Fibroblast Growth Factor-10
A SECOND CANDIDATE STROMAL TO EPITHELIAL CELL ANDROMEDIN IN PROSTATE*
- From the Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A&M University System Health Science Center and Department of Biochemistry and Biophysics, Texas A&M University, Houston, Texas 77030-3303
Abstract
Fibroblast growth factor (FGF)-10, a homologue of FGF-7, is expressed significantly in normal rat prostate tissue, well differentiated rat prostate tumors with an epithelial and stromal compartment and only in derived prostate stromal cells in culture. Similar to FGF-7, recombinant rat FGF-10 was a specific mitogen for prostate epithelial cells. In contrast to FGF-7 which is widely expressed among stromal cells in tissues, the expression of FGF-10 correlated with the presence of stromal cells of muscle origin. Radioreceptor binding assays and covalent cross-linking analysis revealed that FGF-10 binds with an affinity equal to FGF-7 to resident epithelial cell receptor, FGFR2IIIb, but unlike FGF-7 also binds the IIIb splice variant of FGFR1. Analysis of mRNA expression by RNase protection revealed that, similar to FGF-7, the expression of FGF-10 was responsive to androgen in stromal cells from normal prostate and non-malignant differentiated tumors. Although FGF-10 cDNA exhibits a signal sequence for secretion, cultured stromal cells exhibit strictly a cell-associated FGF-10 antigen that correlates with an alternately translated intracellular isoform. FGF-10 requires 1.4 times higher NaCl for elution from immobilized heparin than does FGF-7 and binds to four times the number of sites on the pericellular matrix of epithelial cells. The results show that prostate stromal cell-derived FGF-10, like FGF-7, exhibits the properties of an andromedin which may indirectly mediate control of epithelial cell growth and function by androgen. Although FGF-10 and FGF-7 bind and activate the same resident epithelial cell receptor (FGFR2IIIb), differences in cell type of origin, compartmentation by alternate translation, the affinity for FGFR1IIIb, and access to FGFR by differential interaction with pericellular matrix heparan sulfate suggest they may play both independent and compensatory roles in prostate homeostasis.
Footnotes
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↵* This work was supported by United States Public Health Service Grants DK40739 and DK35310 from the NIDDK, National Institutes of Health, and NCI, National Institutes of Health, Grant CA59971.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Contributed equally to the results of this work.
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↵§ To whom correspondence should be addressed: Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 W. Holcombe Blvd., Houston, TX 77030-3303. Tel.: 713-677-7522; Fax: 713-677-7512; E-mail: wmckeeha{at}ibt.tamu.edu.
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↵2 W. Lu, Y. Luo, M. Kan, and W. L. McKeehan, unpublished results.
- Abbreviations:
- FGF
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fibroblast growth factor
- FGFR
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FGF receptor kinase
- FGFR1–4
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type 1 through 4 of the FGFR kinases
- PAGE
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polyacrylamide gel electrophoresis
- PCR
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polymerase chain reaction
- NIH 3T3
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fibroblast-like mesenchymal cells
- NP
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normal prostate
- DT-E
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Dunning tumor epithelial cells
- DT-S
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Dunning tumor stromal cells
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- Received September 25, 1998.
- Revision received December 21, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
