Expression of basic fibroblast growth factor correlates with resistance to paclitaxel in human patient tumors.
BACKGROUND: Preclinical results indicate acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) present in solid tumors as a cause of broad-spectrum chemoresistance, whereas earlier clinical studies suggest that bFGF expression is associated with opposing outcomes in patients. We investigated the relationship between FGF expression and paclitaxel activity in tumors from bladder, breast, head and neck, ovarian, and prostate cancer patients. MATERIALS AND METHODS: Tumors (n = 96) were maintained in three-dimensional histocultures, retaining tumor-stromal interaction. Bladder tumors were treated with paclitaxel for 2 h, and the other tumors for 24 h. Antiproliferative and proapoptotic effects of paclitaxel were quantified and correlated with expression of aFGF, bFGF, P-glycoprotein (Pgp), p53, and bcl-2. RESULTS: Fifty-one percent (49/96) and 63% (61/96) of tumors showed aFGF and bFGF staining, respectively. aFGF expression was positively correlated with tumor stage (p < 0.01), and bFGF expression with tumor grade and Pgp expression (p < 0.05). Paclitaxel inhibited antiproliferation in 86% of tumors (83/96), with an average inhibition of 46 +/- 19% (mean +/- SD) in the responding tumors. Paclitaxel also induced apoptosis in 96% of tumors (92/96), with an average apoptotic index of 12 +/- 7% in the responding tumors. aFGF expression did not correlate with tumor sensitivity to paclitaxel, whereas bFGF expression showed an inverse correlation (p < 0.01). bFGF expression was a stronger predictor of paclitaxel resistance compared to Pgp, p53, or Bcl-2. CONCLUSION: These results support a role of bFGF in paclitaxel resistance in human patient tumors.
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Pgp aFGF bFGF bFGF Pgp p53 Bcl-2 bFGF bFGF FGF Paclitaxel acidic fibroblast growth factor aFGF aFGF bFGF P-glycoprotein Pgp p53 bcl-2 basic FGF aFGF Paclitaxel bFGF aFGF bFGF bFGF basic fibroblast growth factor paclitaxel paclitaxel paclitaxel paclitaxel paclitaxel paclitaxel paclitaxel