VEGF(A protein that promotes angiogenesis and is known to be a prognostic factor in several types of tumour) in ovarian cancer
Ovarian cancers express high levels of VEGF. Studies of the effects of VEGF in ovarian cancer have shown that it is involved in some of the key features of the disease
- Preclinical data indicate that VEGF is involved in the switch in cell growth from a benign to a malignant growth pattern during the initial development of ovarian cancer1
Switch from a benign to a malignant growth pattern during ovarian cancer development1
The switch from a benign to a malignant growth pattern is an early event in the development of ovarian cancer and one that, based on preclinical data, is mediated at least in part by VEGF.1
- Stimulating the formation of the multiple, small metastases on the peritoneum (the process of peritoneal seeding) that is one of the characteristic features of ovarian cancer2,3
Formation of metastases typical of ovarian cancer on the peritoneum2
The formation of multiple, small metastases on the peritoneum is a characteristic development in ovarian cancer, a process that is promoted by VEGF.2
- Promotion of the increased permeability of tumour(An abnormal growth of cells, forming a mass of tissue) blood vessels, resulting in increased fluid leakage and ultimately the formation of ascites.3–7
Accumulation of ascites, by increasing peritoneal blood vessel permeability3–7
The accumulation of ascites in the abdomen of women with ovarian cancer is a characteristic feature of the disease; ascites is promoted by VEGF, which increases the permeability of blood vessels in peritoneal metastases.3–7
A positive correlation between ascites volume and VEGF concentration has been demonstrated in a mouse model of ovarian cancer.7
Correlation between volume of ascites and VEGF concentration in ovarian cancer7
The graph shows a correlation between the volume of ascites and VEGF concentration in mice bearing human ovarian carcinoma xenografts that were assessed for biologically active VEGF.7
VEGF is associated with aggressive disease in women with ovarian cancer
Several studies have implicated VEGF expression in ovarian cancer with aggressive disease.
First, ovarian malignancy(The tendency of a medical condition, especially tumours, to become progressively worse and to potentially result in death) is associated with elevated VEGF levels in ovarian cyst fluid, and these have been linked to higher rates of tumour recurrence.8
Second, VEGF is an important survival factor for endothelial cells exposed to chemical stress. Carboplatin, which is widely used in ovarian cancer therapy, has been shown to significantly increase VEGF expression and this reduces sensitivity to the agent.9
Finally, high microvascular density(A widely applied morphologic measure of vascularisation), a consequence of VEGF signalling, has been shown to correlate with the biological aggressiveness of ovarian tumours.10
These observations provide support for the targeting of VEGF signalling as a rational approach to ovarian cancer therapy.
References
- Schumacher JJ, Dings RPM, Cosin J, et al. Cancer Res 2007;67:3683–90.
- Zhang L, Yang N, Garcia JR, et al. Am J Pathol 2002;161:2295–309.
- Ramakrishnan S, Subramanian IV, Yokoyama Y, et al. Angiogenesis. 2005;8:169–82.
- Schumacher JJ, Dings RPM, Cosin J, et al. Cancer Res 2007;67:3683–90.
- Zhang L, Yang N, Garcia JR, et al. Am J Pathol 2002;161:2295–309.
- Trinh XB, Tjama WAA, Vermeulen PB, et al. Br J Cancer 2009;100:971–8.
- Belotti D, Paganoni P, Manenti L, et al. Cancer Res 2003;63:5224–9.
- Hazelton D, Nicosia RF, Nicosia SV. Clin Cancer Res 1999;5:823–9.
- Wild R, Dings RPM, Subramanian I, Ramakrishnan S. Int J Cancer 2004;110:343–51.
- Alvarez AA, Krigman HR, Whitaker RS, et al. Clin Cancer Res 1999;5:587–91.