Expression of basic fibroblast growth factor is necessary but insufficient for production of metastasis

Rakesh K. Singh, Reuven Reich, Robert Radinsky, Karen K. Berry, Bhavana J. Dave, Isaiah J. Fidler

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We determined whether overexpression of basic fibroblast growth factor (bFGF) is necessary for enhanced growth and production of metastasis by murine K-1735 melanoma cells. The bFGF gene was transfected into three nonmetastatic clones (C-10, C-19, and C-23) that do not express bFGF mRNA and protein and one metastatic clone that expresses high levels of bFGF mRNA and protein. Control cells were transfected with a dominant selectable marker neomycin resistance gene (neo). All bFGF-transduced cells expressed bFGF-specific mRNA transcripts and cellular bFGF protein and proliferated in culture with medium containing low concentrations of serum. Anchorage-independent growth in hard agarose was enhanced only in bFGF-transfected nonmetastatic C-10 cells which, subsequent to the transfection, also expressed high levels of collagenase IV/gelatinase A activity. The treatment of C-10, C-19, and C-23 cells with exogenous bFGF induced collagenase IV/gelatinase expression, as did the addition of lysates from C-10/bFGF and C-23/bFGF cells. C-10/bFGF cells (but not C-19/bFGF or C-23/bFGF) produced highly vascular and rapidly growing subcutaneous tumors as well as a high incidence of lung metastasis. These data suggest that overexpression of bFGF is necessary but in itself not sufficient to convert nonmetastatic K-1735 cells to the metastatic phenotype and that enhanced tumorigenicity and metastasis require at least concurrent expression of bFGF and collagenase type IV genes.

Original languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalInternational journal of oncology
Volume10
Issue number1
StatePublished - Jan 1 1997

Fingerprint

Fibroblast Growth Factor 2
Neoplasm Metastasis
Collagenases
Messenger RNA
Clone Cells
Matrix Metalloproteinase 8
Genes
Gelatinases
Proteins
Neomycin
Matrix Metalloproteinase 2
Growth
Sepharose
Transfection
Blood Vessels
Culture Media

Keywords

  • Basic fibroblast growth factor
  • Collagenase IV/Gelatinase
  • Metastatic phenotype
  • Murine K-1735 melanoma cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Expression of basic fibroblast growth factor is necessary but insufficient for production of metastasis. / Singh, Rakesh K.; Reich, Reuven; Radinsky, Robert; Berry, Karen K.; Dave, Bhavana J.; Fidler, Isaiah J.

In: International journal of oncology, Vol. 10, No. 1, 01.01.1997, p. 23-31.

Research output: Contribution to journalArticle

Singh, Rakesh K. ; Reich, Reuven ; Radinsky, Robert ; Berry, Karen K. ; Dave, Bhavana J. ; Fidler, Isaiah J. / Expression of basic fibroblast growth factor is necessary but insufficient for production of metastasis. In: International journal of oncology. 1997 ; Vol. 10, No. 1. pp. 23-31.
@article{97611200736d4384bac519cacfcec74a,
title = "Expression of basic fibroblast growth factor is necessary but insufficient for production of metastasis",
abstract = "We determined whether overexpression of basic fibroblast growth factor (bFGF) is necessary for enhanced growth and production of metastasis by murine K-1735 melanoma cells. The bFGF gene was transfected into three nonmetastatic clones (C-10, C-19, and C-23) that do not express bFGF mRNA and protein and one metastatic clone that expresses high levels of bFGF mRNA and protein. Control cells were transfected with a dominant selectable marker neomycin resistance gene (neo). All bFGF-transduced cells expressed bFGF-specific mRNA transcripts and cellular bFGF protein and proliferated in culture with medium containing low concentrations of serum. Anchorage-independent growth in hard agarose was enhanced only in bFGF-transfected nonmetastatic C-10 cells which, subsequent to the transfection, also expressed high levels of collagenase IV/gelatinase A activity. The treatment of C-10, C-19, and C-23 cells with exogenous bFGF induced collagenase IV/gelatinase expression, as did the addition of lysates from C-10/bFGF and C-23/bFGF cells. C-10/bFGF cells (but not C-19/bFGF or C-23/bFGF) produced highly vascular and rapidly growing subcutaneous tumors as well as a high incidence of lung metastasis. These data suggest that overexpression of bFGF is necessary but in itself not sufficient to convert nonmetastatic K-1735 cells to the metastatic phenotype and that enhanced tumorigenicity and metastasis require at least concurrent expression of bFGF and collagenase type IV genes.",
keywords = "Basic fibroblast growth factor, Collagenase IV/Gelatinase, Metastatic phenotype, Murine K-1735 melanoma cells",
author = "Singh, {Rakesh K.} and Reuven Reich and Robert Radinsky and Berry, {Karen K.} and Dave, {Bhavana J.} and Fidler, {Isaiah J.}",
year = "1997",
month = "1",
day = "1",
language = "English (US)",
volume = "10",
pages = "23--31",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "1",

}

TY - JOUR

T1 - Expression of basic fibroblast growth factor is necessary but insufficient for production of metastasis

AU - Singh, Rakesh K.

AU - Reich, Reuven

AU - Radinsky, Robert

AU - Berry, Karen K.

AU - Dave, Bhavana J.

AU - Fidler, Isaiah J.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - We determined whether overexpression of basic fibroblast growth factor (bFGF) is necessary for enhanced growth and production of metastasis by murine K-1735 melanoma cells. The bFGF gene was transfected into three nonmetastatic clones (C-10, C-19, and C-23) that do not express bFGF mRNA and protein and one metastatic clone that expresses high levels of bFGF mRNA and protein. Control cells were transfected with a dominant selectable marker neomycin resistance gene (neo). All bFGF-transduced cells expressed bFGF-specific mRNA transcripts and cellular bFGF protein and proliferated in culture with medium containing low concentrations of serum. Anchorage-independent growth in hard agarose was enhanced only in bFGF-transfected nonmetastatic C-10 cells which, subsequent to the transfection, also expressed high levels of collagenase IV/gelatinase A activity. The treatment of C-10, C-19, and C-23 cells with exogenous bFGF induced collagenase IV/gelatinase expression, as did the addition of lysates from C-10/bFGF and C-23/bFGF cells. C-10/bFGF cells (but not C-19/bFGF or C-23/bFGF) produced highly vascular and rapidly growing subcutaneous tumors as well as a high incidence of lung metastasis. These data suggest that overexpression of bFGF is necessary but in itself not sufficient to convert nonmetastatic K-1735 cells to the metastatic phenotype and that enhanced tumorigenicity and metastasis require at least concurrent expression of bFGF and collagenase type IV genes.

AB - We determined whether overexpression of basic fibroblast growth factor (bFGF) is necessary for enhanced growth and production of metastasis by murine K-1735 melanoma cells. The bFGF gene was transfected into three nonmetastatic clones (C-10, C-19, and C-23) that do not express bFGF mRNA and protein and one metastatic clone that expresses high levels of bFGF mRNA and protein. Control cells were transfected with a dominant selectable marker neomycin resistance gene (neo). All bFGF-transduced cells expressed bFGF-specific mRNA transcripts and cellular bFGF protein and proliferated in culture with medium containing low concentrations of serum. Anchorage-independent growth in hard agarose was enhanced only in bFGF-transfected nonmetastatic C-10 cells which, subsequent to the transfection, also expressed high levels of collagenase IV/gelatinase A activity. The treatment of C-10, C-19, and C-23 cells with exogenous bFGF induced collagenase IV/gelatinase expression, as did the addition of lysates from C-10/bFGF and C-23/bFGF cells. C-10/bFGF cells (but not C-19/bFGF or C-23/bFGF) produced highly vascular and rapidly growing subcutaneous tumors as well as a high incidence of lung metastasis. These data suggest that overexpression of bFGF is necessary but in itself not sufficient to convert nonmetastatic K-1735 cells to the metastatic phenotype and that enhanced tumorigenicity and metastasis require at least concurrent expression of bFGF and collagenase type IV genes.

KW - Basic fibroblast growth factor

KW - Collagenase IV/Gelatinase

KW - Metastatic phenotype

KW - Murine K-1735 melanoma cells

UR - http://www.scopus.com/inward/record.url?scp=0031024414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031024414&partnerID=8YFLogxK

M3 - Article

C2 - 21533339

AN - SCOPUS:0031024414

VL - 10

SP - 23

EP - 31

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 1

ER -