Direct FGF receptor 1 activation through an anti-idiotypic strategy mimicks the biological activity of FGF-2 and inhibits the progression of the bladder carcinoma derived from NBT-II cells

Malavaud, Bernard; Pedron, Sandrine; Sordello, Sylvie; Mazerolles, Catherine; Billottet, Clotilde; Thiery, Jean Paul; Jouanneau, Jacqueline; Plouët, Jean

doi:10.1038/sj.onc.1207135

Cited by 3 publications

(1 citation statement)

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“…Thus, we could speculate that the angiogenic activity in our model could be inhibited by L-NAME, and that only the fibrotic activity would persist. Interestingly, it has been reported that an anti-idiotypic strategy mimics the biological activity of FGF-2, inhibiting the progression of an experimental bladder cancer [37]. However, further experiments should be performed to clarify the precise role of FGF-2 in response to BCG in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Bacillus Calmette Guerin Induces Fibroblast Activation Both Directly and through Macrophages in a Mouse Bladder Cancer Model

et al. 2010

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BackgroundBacillus Calmette-Guerin (BCG) is the most effective treatment for non-muscle invasive bladder cancer. However, a failure in the initial response or relapse within the first five years of treatment has been observed in 20% of patients. We have previously observed that in vivo administration of an inhibitor of nitric oxide improved the response to BCG of bladder tumor bearing mice. It was described that this effect was due to a replacement of tumor tissue by collagen depots. The aim of the present work was to clarify the mechanism involved in this process.Methodology/Principal FindingsWe demonstrated that BCG induces NIH-3T3 fibroblast proliferation by activating the MAPK and PI3K signaling pathways and also differentiation determined by alpha-smooth muscle actin (alpha-SMA) expression. In vivo, intratumoral inoculation of BCG also increased alpha-SMA and collagen expression. Oral administration of L-NAME enhanced the pro-fibrotic effect of BCG. Peritoneal macrophages obtained from MB49 tumor-bearing mice treated in vivo with combined treatment of BCG with L-NAME also enhanced fibroblast proliferation. We observed that FGF-2 is one of the factors released by BCG-activated macrophages that is able to induce fibroblast proliferation. The involvement of FGF-2 was evidenced using an anti-FGF2 antibody. At the same time, this macrophage population improved wound healing rate in normal mice and FGF-2 expression was also increased in these wounds.Conclusions/SignificanceOur findings suggest that fibroblasts are targeted by BCG both directly and through activated macrophages in an immunotherapy context of a bladder murine model. We also described, for the first time, that FGF-2 is involved in a dialog between fibroblasts and macrophages induced after BCG treatment. The fact that L-NAME administration improves the BCG effect on fibroblasts, NO inhibition, might represent a new approach to add to the conventional BCG therapy.

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Section: Discussionmentioning

confidence: 99%