VEGF expression in ovarian cancer

Early in tumorigenesis, the previously highly maintained balance of pro-angiogenic and anti-angiogenic factors that regulate normal ovarian function is tipped, with the downregulation of anti-angiogenic signaling and the upregulation of pro-angiogenic growth factors.¹ Although VEGF is expressed in healthy ovaries, it is highly expressed in ovarian cancer.^2-4 VEGF expression is hypothesized to mediate multiple functional and structural characteristics of the disease.⁵

In one preclinical model, tumor xenographs highly expressing VEGF-A formed larger cysts lined with tumor cells relative to xenographs that weakly expressed VEGF-A.³ In another study that examined gonadotropin levels, elevated levels of luteinizing hormone and follicle-stimulating hormone increased VEGF expression and significantly contributed to the angiogenic potential of ovarian carcinomas.⁶

The growth of ovarian tumor cells is supplied by ascites, and ascites accumulation is associated with progression.^7,8 Experimental models have demonstrated a positive correlation between ascites volume and VEGF expression.⁸

Correlation between ascites volume and VEGF expression⁸

Adapted with permission from Belotti D, Paganoni P, Manenti L, et al. Cancer Res. 2003;63:5224-5229. Figure 1. In a murine model, a positive correlation was observed between ascites volume and VEGF levels in ascitic fluid. In this same study, a correlation was also observed between ascites volume and tumor burden.

References:

1.

Kumaran GC, Jayson GC, Clamp AR. Br J Cancer. 2009;100:1-7.

2.

Ramakrishnan S, Subramanian IV, Yokoyama Y, Geller M. Angiogenesis. 2005;8:169-182.

3.

Duyndam MC, Hilhorst MC, Schluper HM, et al. Am J Pathol. 2002;160:537-548.

4.

Zhang L, Yang N, Garcia JR, et al. Am J Pathol. 2002;161:2295-2309.

5.

Hefler LA, Mustea A, Konsgen D, et al. Clin Cancer Res. 2007;13:898-901.

6.

Schiffenbauer YS, Abramovitch R, Meir G, et al. Proc Natl Acad Sci U S A. 1997;94:13203-13208.

7.

Alvarez AA, Krigman HR, Whitaker RS, et al. Clin Cancer Res. 1999;5:587-591.

8.

Belotti D, Paganoni P, Manenti L, et al. Cancer Res. 2003;63:5224-5229.