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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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
Pages (from-to)23-31
Number of pages9
JournalInternational Journal of Oncology
Volume10
Issue number1
DOIs
StatePublished - Jan 1997
Externally publishedYes

Keywords

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

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