Vascular endothelial growth factor C gene expression is closely related to invasion phenotype in gynecological tumor cells

Objective. The correlation between the gene expression of various angiogenic factors and in vitro invasive activity in 16 human gynecological cancer cell lines was investigated. Methods. Semiquantitative reverse transcription polymerase chain reaction analysis was performed to investigate the mRNA expression levels of vascular endothelial growth factors (VEGF-A, -B, -C, and -D), basic fibroblast growth factor (bFGF), and matrix metalloproteinase (MMP)-2 with beta -actin coamplified as an internal standard. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. Results. Expression of VEGF-A mRNA was detected in all 16 cell lines, whereas the relative expression levels of other VEGF family members and bFGF, differed markedly among the cell lines. There was a statistical correlation between VEGF-C gene expression and the number of cells that migrated and invaded (P < 0.01). However, expression of mRNAs of other angiogenic factors did not correlate with motility and invasive activity of the cells. Moreover, there was a close correlation between VEGF-C and MMP-2 gene expression levels (P < 0.05). Conclusion. Tumor cells that produce VEGF-C may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers. (C) 2001 Academic Press.