Fibroblast Growth Factor-10

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. 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. Members of the fibroblast growth factor (FGF) 1The abbreviations used are: FGF, fibroblast growth factor; FGFR, FGF receptor kinase; FGFR1–4, type 1 through 4 of the FGFR kinases; PAGE, polyacrylamide gel electrophoresis; PCR, polymerase chain reaction; NIH 3T3, fibroblast-like mesenchymal cells; NP, normal prostate; DT-E, Dunning tumor epithelial cells; DT-S, Dunning tumor stromal cellsfamily which is comprised of 20 or more homologous polypeptides and four tyrosine kinase receptor (FGFR) genes play a role in prostate homeostasis and tumor progression (1McKeehan W.L. Wang F. Kan M. Prog. Nucleic Acids Res. Mol. Biol. 1998; 59: 135-176Crossref PubMed Scopus (363) Google Scholar, 2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google Scholar, 3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar). FGF-1, FGF-2, FGF-3, FGF-5, and FGF-7 and splice variants of FGFR1 and FGFR2 have been implicated. FGF-1, which acts on FGFR isoforms that are both in epithelium and stroma, is expressed in both prostate compartments and expression increases with malignant progression (4Mansson P.E. Adams P. Kan M. McKeehan W.L. Cancer Res. 1989; 49: 2485-2494PubMed Google Scholar). FGF-2, FGF-3, and FGF-5 are expressed ectopically in malignant epithelial cells (3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar). FGF-7, whose expression is limited to the stromal cells, is the androgen-responsive signal of a directionally specific paracrine communication system from stroma to epithelium in normal prostate and non-malignant differentiated tumors with a stromal compartment (3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar). Reception of the stromal signal appears to be mediated by FGFR2IIIb, a mutually exclusive alternate splice variant, which recognizes FGF-7 with high affinity (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google Scholar, 3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar, 5Ornitz D.M. Xu J. Colvin J.S. McEwen D.G. MacArthur C.A. Coulier F. Gao G. Goldfarb M. J. Biol. Chem. 1996; 271: 15292-15297Abstract Full Text Full Text PDF PubMed Scopus (1449) Google Scholar). In progressively malignant prostate tumors, a phenotypic splice switch from expression of the FGFR2IIIb to the FGFR2IIIc isoform occurs with eventual loss of FGFR2 gene expression altogether in some malignant clones (3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar, 6Feng S. Wang F. Matsubara A. Kan M. McKeehan W.L. Cancer Res. 1997; 57: 5369-5378PubMed Google Scholar). Restoration of the FGFR2 kinase to malignant tumor cells restores limitations on growth rates by increased differentiation in response to stroma cells expressing FGF-7 (6Feng S. Wang F. Matsubara A. Kan M. McKeehan W.L. Cancer Res. 1997; 57: 5369-5378PubMed Google Scholar). Therefore, it is thought that in the epithelial cell context, FGFR2 mediates a homeostatic balance through both positive and negative effects on population growth rates and differentiation. This is in contrast to FGFR1, which is a resident FGFR in stromal cells (6Feng S. Wang F. Matsubara A. Kan M. McKeehan W.L. Cancer Res. 1997; 57: 5369-5378PubMed Google Scholar). In this study, we show that, similar to FGF-7, FGF-10 is expressed only in the stroma of normal prostate and differentiated prostate tumors, and that expression is sensitive to androgen. FGF-10 is a mitogen for isolated prostate epithelial cells, but not for stromal cells which express it, and binds specifically to the resident epithelial cell receptor, FGFR2IIIb. FGF-10 differs from FGF-7 by its more restricted expression pattern, the ability to bind FGFR1IIIb in addition to FGFR2IIIb, and in the interaction with heparin and pericellular matrix heparan sulfate. The two factors exhibit potential for both compensatory and specific activities in the prostate. Total RNA was isolated from Dunning R3327PAP rat prostate stromal cells by guanidinium thiocyanate/phenol/chloroform extraction and first strand cDNA was prepared using SuperScript II RNase H Reverse Transcriptase (Life Technologies) with random primers. The polymerase chain reaction (PCR) was carried out for 38 cycles at 94 °C for 1 min, 55 °C for 2 min, and 72 °C for 2 min. Full-length FGF-10 cDNA was generated from the template with which a and an The was and and on a by and II at The cDNA was by with and and with the cDNA was the expression at the and expressed in cells in an expression to at the to of FGF-10 with the at was generated and by a and for of FGF at the with and of the FGF isoform by with immobilized on Y. Kan M. McKeehan W.L. 1998; PubMed Scopus Google Scholar). gel and sequence the of FGF-7 at was by the same Y. Kan M. McKeehan W.L. 1998; PubMed Scopus Google Scholar). was from and from FGF-10 mRNA was in the using and which the sequence FGF-10 cDNA sequence is from that of of and was used to FGF-10 mRNA and which a sequence of rat FGF-7 used for analysis of FGF-7 mRNA Total RNA from and cells in the was to FGF-10 was using the same for the by for analysis of FGF-7 was cycles at 94 °C for 1 min, °C for 2 min, and 72 °C for 2 min. The in cDNA for FGF-7 and FGF-10 and cDNA from RNA of used for positive Analysis of was used an mRNA to and sites in rat FGF-10 cDNA was with and at The template was with and the RNA using RNA polymerase and to a specific of of cDNA template using the FGF-7 mRNA was by protection of a from to (3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar, M. G. Xu J. M. J. In Cell. Biol. 1992; Scopus Google Scholar). 20 of RNA from or cells was with 1 of RNA with RNase for at on polyacrylamide by was used a control for using the protection the expression of FGF-7 and FGF-10, 1 of FGF-7, FGF-10, and (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google in the same RNase protection protection to the same specific and the expression was by of was used the to RNA from the cell and of cells cultured in and with in cell and the cells in the was and the cells to in The from cells was times to and the cell was times from of cell to of The with FGF-10 and by analysis by and recombinant rat FGF-10 was prepared from Y. Kan M. McKeehan W.L. 1998; PubMed Scopus Google Scholar). This antigen was used to which that a of in of isoforms FGFR1IIIb and in cells have been F. Kan M. Xu J. G. McKeehan W.L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The FGFR1IIIb and the cDNA by M. D.M. Xu J. Colvin J.S. McEwen D.G. MacArthur C.A. Coulier F. Gao G. Goldfarb M. J. Biol. Chem. 1996; 271: 15292-15297Abstract Full Text Full Text PDF PubMed Scopus (1449) Google Scholar, D.M. P. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). FGFR1IIIb from was by The was the and sites of from was first and to with and or with with the two at and this was with and to at the the was by The expression FGFR1IIIb and with cells, using the F. Kan M. Xu J. G. McKeehan W.L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). by was carried out (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google Scholar, 3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar, P.E. Adams P. Kan M. McKeehan W.L. Cancer Res. 1989; 49: 2485-2494PubMed Google Scholar, 6Feng S. Wang F. Matsubara A. Kan M. McKeehan W.L. Cancer Res. 1997; 57: 5369-5378PubMed Google Scholar). FGF-1, recombinant FGF-2, FGF-7, and FGF-10 prepared to specific activities of The of specific binding of FGF to FGF receptor kinase sites or heparan sulfate sites in the pericellular matrix was carried out (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google Scholar, 3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar, P.E. Adams P. Kan M. McKeehan W.L. Cancer Res. 1989; 49: 2485-2494PubMed Google Scholar, 6Feng S. Wang F. Matsubara A. Kan M. McKeehan W.L. Cancer Res. 1997; 57: 5369-5378PubMed Google Scholar, M. McKeehan W.L. PubMed Scopus Google Scholar). of FGF using the with of revealed the presence of FGF-10 mRNA in normal rat prostate and the non-malignant well differentiated Dunning R3327PAP tumor 1 in addition to tissue, which was used a positive M. A. S. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). The FGF-10 signal that of FGF-7 in the normal prostate both and of stromal cells from the differentiated tumors from isolated epithelial and stromal cells (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google Scholar, 3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar). Similar to FGF-7, the FGF-10 mRNA not be in isolated epithelial cells from the tumors FGF-7 be in tumors derived from isolated cells they to malignant Dunning tumors and derived cells (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google the FGF-10 was in the same expression of FGF-10 mRNA was limited to the stromal cells of normal prostate and differentiated prostate tumors, we expression of the two in and muscle and mesenchymal cells derived from in which FGF-7 is Although FGF-10 is expressed in M. A. S. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google FGF-10 not be in isolated from to FGF-7 1 with FGF-7, the FGF-10 signal was in cells, which are also thought to be fibroblast-like cells. FGF-7 and FGF-10 in cells. The FGF-7 mRNA was in from tumor sites in rat and FGF-10 was to FGF-7, FGF-10 mRNA was in normal isolated from In contrast to the fibroblast-like cells, the rat muscle cell and a muscle cell from normal rat prostate M. McBride 1996; PubMed Scopus Google the positive of FGF-10 to FGF-7 In contrast to both rat muscle and tissue, which are in muscle cells, FGF-10 equal to or than FGF-7 and FGF-10 in cells and the prostate tumor epithelial cell results show that, similar to FGF-7, the expression of FGF-10 is with the stromal or mesenchymal compartment of prostate and a number of the expression of FGF-10 is more restricted than that of FGF-7 and may with muscle cell to the stromal or mesenchymal cell population in the and derived tumors. that the results and more than of FGF-7 and FGF-10 the mRNA for the two factors in prostate and derived cells by protection The results the The more analysis that the of expression of FGF-7 to FGF-10 mRNA in was but that of FGF-10 increased in the tumors and derived cells in an expression of for the two tumors and cells to expression of FGF-10 is FGF-7 at 2 and Although an FGF-7 signal be by in at the of 1 of the tumors in control expression of both FGF-7 and FGF-10 was the of by the protection 2 of FGF-7 and FGF-10 mRNA in prostate cells and RNA from the prostate cells and was by protection with the same of FGF-7, FGF-10, and RNA to the same specific in the same reaction of the in was in by expression to The of the of was of the FGF-7 and FGF-10 in was by by the of the in the by the of The of the FGF-7 from cells FGF-10, was a of and expressed a of that The is of independent in a Total RNA from the prostate cells and was by protection with the same of FGF-7, FGF-10, and RNA to the same specific in the same reaction of the in was in by expression to The of the of was of the FGF-7 and FGF-10 in was by by the of the in the by the of The of the FGF-7 from cells FGF-10, was a of and expressed a of that The is of independent the expression of FGF-10 mRNA was responsive to androgen for FGF-7, cultured stromal cells from both normal prostate and the androgen-responsive Dunning R3327PAP tumor isolated and (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google Scholar, 3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar). in in the or presence of for and RNA was isolated and by protection 2 of FGF-10 mRNA in of stromal cells from normal rat prostate was on androgen. analysis of that the expression of FGF-10 mRNA by in both and cultured of stromal cells from tumors. for FGF-7, stromal cells by an of expression of FGF-10, which with of culture. on the control mRNA be in this Y. G. McKeehan W.L. In Cell. Biol. Scopus Google Scholar). FGF-10 mRNA to FGF-10 the of the cultured tumor stromal cells was and by and with prepared recombinant FGF-10 from FGF-10 antigen from to stromal cells from the tumors was the of extraction and analysis of the cell with NaCl and revealed a at from that not be in of the epithelial cells This is than the recombinant FGF-10 at which was to at recombinant FGF-10 at which at Y. Kan M. McKeehan W.L. 1998; PubMed Scopus Google which by of is also rat FGF-10 was generated by a for and of FGF polypeptides in in Y. Kan M. McKeehan W.L. 1998; PubMed Scopus Google Scholar). that FGF-10 at of at 1 in non-malignant rat prostate tumor epithelial cells which was than the of FGF-10 FGF-7 of stromal cells from the same tumors in which both factors are binding assays using which and to on both and cells that FGF-7 and FGF-10 to equal with to the epithelial cells, but both to with to stromal cells that the and of FGF-10 with the binding of binding to cell FGF-10 was with the and the by and FGF-1, FGF-7, and FGF-10 at and from cells which the FGFR and a from J. M. Y. M. Kan M. J. McKeehan W.L. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). FGF-7 FGF-10 to FGFR on the stromal cells at times higher and of the affinity cross-linking of FGF-10 to epithelial cell The to and cells by addition of and analysis The positive to potential of to cells or FGF-7 and FGF-10 to FGFR1IIIb and FGFR2IIIb and and and expressed on the of cells and the ability of FGF-10 to with the binding of which binds to isoforms in the presence of FGF-10 with to cells expressing recombinant FGFR1IIIb and FGFR2IIIb with an to of of and was with to cells expressing and affinity cross-linking analysis revealed that the binding to cells expressing FGFR2IIIb and FGFR1IIIb was to that to the recombinant FGFR FGF-7 and FGF-10 with for binding to recombinant FGFR2IIIb expressed in cells at and with the or the was the and results suggest that are FGF-10 and FGF-7 exhibit equal for of FGF-10 and FGF-7 for binding to FGFR2IIIb. cells expressing FGFR2IIIb with the FGF in the presence of of FGF-7 or FGF-10 Similar to of the FGF FGF-10 exhibits affinity for which be in its and and heparan sulfate In contrast to FGF-7, which from immobilized heparin at FGF-10 at which is similar to This is the that is to from the same analysis of the binding of FGF-7 and FGF-10 to pericellular matrix which are to be heparan sulfate sites on epithelial cells, revealed that FGF-10 binds to 1 sites FGF-7 binds to sites cell factors exhibit a similar affinity to the pericellular matrix we show that, similar to FGF-7, expression of FGF-10 is restricted to stromal cells of normal prostate and androgen-responsive differentiated non-malignant prostate tumors. FGF-10 mRNA on androgen in cells from normal prostate and responsive in stromal cells from a well differentiated In recombinant FGF-10 specifically epithelial cells and binds specifically to the resident epithelial cell FGFR splice variant, FGFR2IIIb, with similar affinity to FGF-10 a FGF that is in a paracrine system from prostate stroma to cells exhibit response to FGF-7 or for FGF-7, FGF-10 is also a in of the of androgen in the stroma to epithelial cells (2Yan G. Fukabori Y. Nikolaropolous S. Wang F. McKeehan W.L. Mol. Endocrinol. 1992; 6: 2123-2128Crossref PubMed Scopus (257) Google Scholar, 3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar). The FGF-10 cDNA a of which exhibits a signal the of in the of in a M. A. S. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). In of the cDNA two M. A. S. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, J. S. 1997; PubMed Scopus Google Scholar). In with a which FGF-10 by in cells J. S. 1997; PubMed Scopus Google FGF-10 antigen not be in the of cultured prostate stromal cells from differentiated non-malignant tumors which express the FGF-10 with an recombinant antigen revealed a with of 20 in of the stromal cells that not be in an of from epithelial cells. for the analysis that 1 of FGF-10 antigen is with This was than the FGF-10 which is the to by of the signal Although the FGF-10 may by an from a higher which been to in addition to J. S. 1997; PubMed Scopus Google it also may be an alternately translated at with of by alternately translated intracellular is with the from in M. A. S. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, J. S. 1997; PubMed Scopus Google the presence of a of FGF-10 antigen in cell and the by of the prostate stromal cell FGF-3, which exhibits similar receptor to FGF-10 Y. Kan M. McKeehan W.L. 1998; PubMed Scopus Google also exhibits and intracellular isoforms to alternate M. P. J. Biol. Chem. 1997; PubMed Scopus Google Scholar). the that of FGF-10 is also at the of alternate and of the from prostate stromal cells requires the in and from epithelial cells. the in function in the expression of FGF-10 appears more restricted than FGF-7, which is expressed in the stromal or mesenchymal compartment of and J.S. M. Biol. PubMed Scopus Google Scholar). FGF-10 was first in rat using homologous to and FGF-7, and to be expressed only in and Y. M. M. Mol. Res. 1997; PubMed Scopus Google Scholar). that FGF-10 was expressed at in specific of the A. A. Y. M. S. 1997; PubMed Google and in the in the A. A. Y. M. S. 1997; PubMed Google Scholar). that expression of the FGF-10 mRNA is more restricted than FGF-7 in and cells in the Although the FGF-10 to FGF-7 is in fibroblast-like cells, expression of FGF-10 was equal to or than that of FGF-7 in prostate stromal cells which are thought to of muscle cells. The presence of of FGF-10 to FGF-7 in rat prostate muscle cells and in muscle cells to suggest that the stromal cells from the Dunning R3327PAP tumors (4Mansson P.E. Adams P. Kan M. McKeehan W.L. Cancer Res. 1989; 49: 2485-2494PubMed Google Scholar, and to the of from the tumor stroma than stroma from the in the (4Mansson P.E. Adams P. Kan M. McKeehan W.L. Cancer Res. 1989; 49: 2485-2494PubMed Google Scholar, 6Feng S. Wang F. Matsubara A. Kan M. McKeehan W.L. Cancer Res. 1997; 57: 5369-5378PubMed Google Scholar). Although we the that FGF-10 expression is in by presence of the tumor or stroma that the FGF-10 expression was or in from results we that FGF-10 be a to muscle cells in stromal cell In similar to normal prostate that a well epithelial and stromal FGF-10 is only in tumors that exhibit both This both the tumor and tumors which with isolated epithelial and stromal cells derived from the tumors. tumors, which are at first and differentiated epithelial cells by stroma, but also exhibit of cells (3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google express a significantly of FGF-7 to FGF-7 was in tumors derived from tumor epithelial cells which are of stroma the tumor and the malignant tumors that from tumors, which exhibit FGF-7 have a stromal The that isolated and cells derived from the malignant tumors in exhibit FGF-7 mRNA that FGF-7, but not FGF-10, may be in epithelial cells the to The of FGF-7 for the resident epithelial cell FGFR2IIIb isoform the specific of the FGF polypeptides to show that FGF-7 and FGF-10 specifically and with the resident FGFR isoforms on prostate epithelial cells with equal on the prostate stromal cells which not express FGFR2IIIb be at to This is in contrast to a which that FGF-10 was only FGF-7 in of in and that FGF-10 in at than M. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). Although FGF-10 an equal affinity for recombinant FGFR2IIIb, in contrast to FGF-7, it the FGFR1IIIb but was times in from FGFR1IIIb than from FGFR2IIIb. In this FGF-10 appears to be similar to which a response in cells the FGFR1IIIb well the FGFR2IIIb D.M. Xu J. Colvin J.S. McEwen D.G. MacArthur C.A. Coulier F. Gao G. Goldfarb M. J. Biol. Chem. 1996; 271: 15292-15297Abstract Full Text Full Text PDF PubMed Scopus (1449) Google Scholar). analysis of expression of FGFR1IIIb to in the prostate and cells in this is we have that the of resident FGFR2 gene and the of FGFR1 in prostate tumor epithelial cells with progression to (3Yan G. Fukabori Y. McBride G. Nikolaropolous S. McKeehan W.L. Mol. Cell. Biol. 1993; 13: 4513-4522Crossref PubMed Scopus (380) Google Scholar, 6Feng S. Wang F. Matsubara A. Kan M. McKeehan W.L. Cancer Res. 1997; 57: 5369-5378PubMed Google Scholar). the FGFR1IIIb isoform is of the of the FGFR1 gene in epithelial cells, FGF-10, which to homeostasis of the epithelial cell population through resident FGFR2IIIb, may to malignant analysis of FGFR1IIIb expression in rat prostate that expression of the isoform is in the differentiated tumors with well stromal but not in malignant tumors with Y. M. and of the cell type expressing the FGFR1IIIb variant is and or pericellular matrix heparan sulfate play roles in and control of access of FGF to FGFR (1McKeehan W.L. Wang F. Kan M. Prog. Nucleic Acids Res. Mol. Biol. 1998; 59: 135-176Crossref PubMed Scopus (363) Google and an role a of the FGFR M. Wang F. Xu J. J. McKeehan W.L. 1993; PubMed Scopus Google Scholar, M. Wang F. Kan M. McKeehan W.L. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). In contrast to FGF-1, the of FGF-7 on epithelial cells is by heparin M. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, Wang F. Kan M. In Cell. Biol. 1997; PubMed Scopus Google the binding of FGF-7 to isolated FGFR2IIIb is on heparin similar to Wang F. Kan M. In Cell. Biol. 1997; PubMed Scopus Google Scholar). In the assays and in this study, we of heparin on the of FGF-1, FGF-7, or FGF-10 for prostate epithelial cells at to for FGF-7 and FGFR2IIIb Wang F. Kan M. In Cell. Biol. 1997; PubMed Scopus Google heparin was for the binding of to recombinant FGFR expressed on the of cells or isolated and immobilized FGFR not results show that FGF-10 a higher affinity for immobilized heparin than does FGF-7 and that the pericellular matrix of epithelial cells exhibits 4 times more binding sites for FGF-10 than for Although this is not a differential or binding the the results suggest that heparan sulfate may access or affinity of the two for FGFR2IIIb specific in the have that the heparan sulfate of the FGFR heparan sulfate FGF that bind to the in contrast to which is an of pericellular matrix heparan sulfate M. Wang F. McKeehan W.L. J. Biol. Chem. Scholar). In FGF-7 and FGF-10 are in to stromal origin, to androgen and the binding and of epithelial cells through FGFR2IIIb, the differential expression among stromal cell the differential interaction with pericellular heparan sulfate and the affinity of FGF-10 for FGFR1IIIb may roles on the two in a M. for FGFR1IIIb and of for the cell and Kan for