Expression of the VEGF/VEGFR2 Regulated Fatty Acid Binding Protein 4 (FABP4) in Endothelial Cells of Ovarian Carcinomas and Metastasis
K Gwin, E Lengyel, S Dogan, R Buell-Gutbrod. University of Chicago, Chicago, IL
Background: FABP4 is a member of the FABP family consisting of nine highly conserved cytosolic proteins that are expressed in a tissue-specific manner. They play an important role in uptake and trafficking of intracellular fatty acids as well as in gene expression, cell proliferation and differentiation. FABP4 has been primarily regarded as an adipocyte- and macrophage specific protein, but there is mounting evidence that it is also a regulator of cell proliferation in certain types of endothelial cells. Recent studies suggest that this endothelial FABP4 expression is regulated by the VEGF (Vascular endothelial growth factor)/VEGFR2 pathway. We hypothesized that FABP4 also has a function in endothelial cells of vasculature supplying ovarian carcinoma and their omental metastases.
Design: Archival paraffin embedded material of 18 serous ovarian carcinomas with corresponding omental metastases were examined by IHC for the expression and localization of FABP4 in the vasculature. Staining was evaluated in the endothelial cells of the primary carcinoma, ovarian stroma, omental fat, desmoplastic tumor interface and omental metastatic tumor.
Results: The endothelial cells in vessels associated with the primary ovarian tumor and omental tumor metastases did not express FABP4 (18/18 cases). Strong cytoplasmic and nuclear expression of FABP4 was observed in endothelial cells of capillaries and small veins in the ovarian stroma adjacent to the carcinoma as well as in the desmoplastic tumor interface of the omental metastases (18/18 cases).
Conclusions: Expression of FABP4 in endothelial cells was confined to capillaries and small veins, which is the main angiogenic component of the vasculature. Small vessels in the direct vicinity of the tumor stained for FABP4 while no vessels of any size associated with serous carcinoma or carcinoma metastasis expressed it. VEGF is the key regulator for angiogenesis under both physiologic and pathologic conditions, and FABP4 is a known target of the activated VEGF/VEGFR2 pathway. Our findings suggest that FABP4 might have an important role in the survival and proliferation of ovarian tumor cells as well as for successful metastatic growth by helping to provide the necessary microvascular supply via angiogenesis. This is of interest, as in addition to the already available VEGF-inhibitors, selective FABP4 inhibitors are currently investigated as treatment options.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 234, Wednesday Morning