Pharmacological inhibition of FGF receptor signaling inhibits LNCaP prostate tumor growth, promatrilysin, and PSA expression

Thirupandiyur Udayakumar, Elisabeth L. Bair, Raymond B. Nagle, G. Timothy Bowden

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Previously we have shown that the matrix metalloproteinase matrilysin (MMP-7) is overexpressed in human prostate cancers compared with normal epithelium. However, the mechanism for this overexpression is not understood. Human prostate fibroblasts have been shown to express certain fibroblast growth factors (FGFs), including FGF-1. Evidence from our laboratory and others has indicated that FGFs can regulate the expression of certain matrix metalloproteinases, including matrilysin. The goal of this study was to determine whether pharmacological inhibition of FGFR signaling would alter LNCaP tumor growth as well as expression of promatrilysin when LNCaP cells were co-injected subcutaneously with human prostate fibroblasts into athymic nude mice. For these inhibitor studies, AG1-X2 beads were coated with the pharmacological FGFR inhibitor SU5402 and were co-injected along with LNCaP and human prostate fibroblast cells (PF). Mice injected with LNCaP/PF and LNCaP/PF/beads alone demonstrated significant tumor growth, whereas mice injected with LNCaP/PF/SU5402-coated beads showed a significant decrease in tumor volume and weight. Immunohistochemical analysis showed that significant promatrilysin expression in tumors was inhibited by the FGFR inhibitor SU5402. Serum prostate-specific antigen (PSA) and promatrilysin levels were measured by enzyme-linked immunosorbent assay. The mice injected with LNCaP/PF and LNCaP/PF/beads expressed promatrilysin and serum PSA levels that were inhibited by co-injecting with SU5402. Therefore, pharmacological inhibition of FGF receptor signaling results in a decrease in the growth of LNCaP tumors generated subcutaneously by co-injecting LNCaP cells and human prostate fibroblasts. The inhibition in tumor growth was correlated with a decrease in tumor promatrilysin expression and a decrease in serum promatrilysin and PSA.

Original languageEnglish (US)
Pages (from-to)70-77
Number of pages8
JournalMolecular Carcinogenesis
Volume38
Issue number2
DOIs
StatePublished - Oct 2003
Externally publishedYes

Fingerprint

Fibroblast Growth Factor Receptors
Prostate-Specific Antigen
Prostate
Fibroblasts
Pharmacology
Growth
Neoplasms
Matrix Metalloproteinases
Matrix Metalloproteinase 7
Fibroblast Growth Factors
Tumor Burden
Nude Mice
Serum
promatrilysin
Fibroblast Growth Factor 1
Prostatic Neoplasms
Epithelium
Enzyme-Linked Immunosorbent Assay
SU 5402

Keywords

  • Fibroblast
  • LNCaP
  • Matrilysin
  • Prostate
  • SU5402
  • Tumor

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Pharmacological inhibition of FGF receptor signaling inhibits LNCaP prostate tumor growth, promatrilysin, and PSA expression. / Udayakumar, Thirupandiyur; Bair, Elisabeth L.; Nagle, Raymond B.; Bowden, G. Timothy.

In: Molecular Carcinogenesis, Vol. 38, No. 2, 10.2003, p. 70-77.

Research output: Contribution to journalArticle

Udayakumar, Thirupandiyur ; Bair, Elisabeth L. ; Nagle, Raymond B. ; Bowden, G. Timothy. / Pharmacological inhibition of FGF receptor signaling inhibits LNCaP prostate tumor growth, promatrilysin, and PSA expression. In: Molecular Carcinogenesis. 2003 ; Vol. 38, No. 2. pp. 70-77.
@article{7cb791eb24204861a55339b0048906d6,
title = "Pharmacological inhibition of FGF receptor signaling inhibits LNCaP prostate tumor growth, promatrilysin, and PSA expression",
abstract = "Previously we have shown that the matrix metalloproteinase matrilysin (MMP-7) is overexpressed in human prostate cancers compared with normal epithelium. However, the mechanism for this overexpression is not understood. Human prostate fibroblasts have been shown to express certain fibroblast growth factors (FGFs), including FGF-1. Evidence from our laboratory and others has indicated that FGFs can regulate the expression of certain matrix metalloproteinases, including matrilysin. The goal of this study was to determine whether pharmacological inhibition of FGFR signaling would alter LNCaP tumor growth as well as expression of promatrilysin when LNCaP cells were co-injected subcutaneously with human prostate fibroblasts into athymic nude mice. For these inhibitor studies, AG1-X2 beads were coated with the pharmacological FGFR inhibitor SU5402 and were co-injected along with LNCaP and human prostate fibroblast cells (PF). Mice injected with LNCaP/PF and LNCaP/PF/beads alone demonstrated significant tumor growth, whereas mice injected with LNCaP/PF/SU5402-coated beads showed a significant decrease in tumor volume and weight. Immunohistochemical analysis showed that significant promatrilysin expression in tumors was inhibited by the FGFR inhibitor SU5402. Serum prostate-specific antigen (PSA) and promatrilysin levels were measured by enzyme-linked immunosorbent assay. The mice injected with LNCaP/PF and LNCaP/PF/beads expressed promatrilysin and serum PSA levels that were inhibited by co-injecting with SU5402. Therefore, pharmacological inhibition of FGF receptor signaling results in a decrease in the growth of LNCaP tumors generated subcutaneously by co-injecting LNCaP cells and human prostate fibroblasts. The inhibition in tumor growth was correlated with a decrease in tumor promatrilysin expression and a decrease in serum promatrilysin and PSA.",
keywords = "Fibroblast, LNCaP, Matrilysin, Prostate, SU5402, Tumor",
author = "Thirupandiyur Udayakumar and Bair, {Elisabeth L.} and Nagle, {Raymond B.} and Bowden, {G. Timothy}",
year = "2003",
month = "10",
doi = "10.1002/mc.10146",
language = "English (US)",
volume = "38",
pages = "70--77",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Pharmacological inhibition of FGF receptor signaling inhibits LNCaP prostate tumor growth, promatrilysin, and PSA expression

AU - Udayakumar, Thirupandiyur

AU - Bair, Elisabeth L.

AU - Nagle, Raymond B.

AU - Bowden, G. Timothy

PY - 2003/10

Y1 - 2003/10

N2 - Previously we have shown that the matrix metalloproteinase matrilysin (MMP-7) is overexpressed in human prostate cancers compared with normal epithelium. However, the mechanism for this overexpression is not understood. Human prostate fibroblasts have been shown to express certain fibroblast growth factors (FGFs), including FGF-1. Evidence from our laboratory and others has indicated that FGFs can regulate the expression of certain matrix metalloproteinases, including matrilysin. The goal of this study was to determine whether pharmacological inhibition of FGFR signaling would alter LNCaP tumor growth as well as expression of promatrilysin when LNCaP cells were co-injected subcutaneously with human prostate fibroblasts into athymic nude mice. For these inhibitor studies, AG1-X2 beads were coated with the pharmacological FGFR inhibitor SU5402 and were co-injected along with LNCaP and human prostate fibroblast cells (PF). Mice injected with LNCaP/PF and LNCaP/PF/beads alone demonstrated significant tumor growth, whereas mice injected with LNCaP/PF/SU5402-coated beads showed a significant decrease in tumor volume and weight. Immunohistochemical analysis showed that significant promatrilysin expression in tumors was inhibited by the FGFR inhibitor SU5402. Serum prostate-specific antigen (PSA) and promatrilysin levels were measured by enzyme-linked immunosorbent assay. The mice injected with LNCaP/PF and LNCaP/PF/beads expressed promatrilysin and serum PSA levels that were inhibited by co-injecting with SU5402. Therefore, pharmacological inhibition of FGF receptor signaling results in a decrease in the growth of LNCaP tumors generated subcutaneously by co-injecting LNCaP cells and human prostate fibroblasts. The inhibition in tumor growth was correlated with a decrease in tumor promatrilysin expression and a decrease in serum promatrilysin and PSA.

AB - Previously we have shown that the matrix metalloproteinase matrilysin (MMP-7) is overexpressed in human prostate cancers compared with normal epithelium. However, the mechanism for this overexpression is not understood. Human prostate fibroblasts have been shown to express certain fibroblast growth factors (FGFs), including FGF-1. Evidence from our laboratory and others has indicated that FGFs can regulate the expression of certain matrix metalloproteinases, including matrilysin. The goal of this study was to determine whether pharmacological inhibition of FGFR signaling would alter LNCaP tumor growth as well as expression of promatrilysin when LNCaP cells were co-injected subcutaneously with human prostate fibroblasts into athymic nude mice. For these inhibitor studies, AG1-X2 beads were coated with the pharmacological FGFR inhibitor SU5402 and were co-injected along with LNCaP and human prostate fibroblast cells (PF). Mice injected with LNCaP/PF and LNCaP/PF/beads alone demonstrated significant tumor growth, whereas mice injected with LNCaP/PF/SU5402-coated beads showed a significant decrease in tumor volume and weight. Immunohistochemical analysis showed that significant promatrilysin expression in tumors was inhibited by the FGFR inhibitor SU5402. Serum prostate-specific antigen (PSA) and promatrilysin levels were measured by enzyme-linked immunosorbent assay. The mice injected with LNCaP/PF and LNCaP/PF/beads expressed promatrilysin and serum PSA levels that were inhibited by co-injecting with SU5402. Therefore, pharmacological inhibition of FGF receptor signaling results in a decrease in the growth of LNCaP tumors generated subcutaneously by co-injecting LNCaP cells and human prostate fibroblasts. The inhibition in tumor growth was correlated with a decrease in tumor promatrilysin expression and a decrease in serum promatrilysin and PSA.

KW - Fibroblast

KW - LNCaP

KW - Matrilysin

KW - Prostate

KW - SU5402

KW - Tumor

UR - http://www.scopus.com/inward/record.url?scp=0141885142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141885142&partnerID=8YFLogxK

U2 - 10.1002/mc.10146

DO - 10.1002/mc.10146

M3 - Article

C2 - 14502646

AN - SCOPUS:0141885142

VL - 38

SP - 70

EP - 77

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 2

ER -