Keratinocyte growth factor-induced motility of breast cancer cells

Endogenous growth factors and cytokines are known to have a major influence on the progression, motility and invasiveness of tumor cells. We have repo rted previously that conditioned media from mouse fibroblasts increases the motility of breast cancer cells. Further, we determined that keratinocyte growth factor (KGF) was an active factor from mouse fibroblasts responsible for most of the motility response in breast cancer cells. The present stud y examined the effect of human KGF on the motility of estrogen receptor (ER )-positive and ER-negative human breast cancer cell lines in culture using time-lapse videomicroscopy to quantify cell motility. In the present study we observed that recombinant human KGF enhanced several parameters of cellu lar motility in ER-positive cells but not in ER-negative cell lines. Furthe r, we observed that the level of KGF receptor (KGFR) expression in ER-posit ive cells was much greater than in the ER-negative cell lines. The motility response to KGF was found to be both dose-and time-dependent. Of the three ER-positive breast cancer cell lines tested, MCF-7 cells were the most res ponsive to KGF stimulation. Finally, MCF-7 cells grown in estrogen-depleted media did not respond to KGF. These results suggest that KGF from stromal tissue surrounding a primary tumor mass can enhance tumor cell motility and may be an early signal in the progression of breast cancer cells to a more motile and metastatic phenotype. Thus, KGF, KGFR and/or the KGF signaling pathway may be important therapeutic targets for the treatment or preventio n of breast cancer metastasis.