Melanoma is a common neoplastic disorder in dogs with variable presentation and biological behaviour. Melanomas acoount for 9-20% of all skin tumors and are the most common tumor in the oral cavitiy and the digits (Goldschmidt et al., 1985). Cutaneous melanoma is generally a benign condition and surgical excision is curative in many cases; but oral and subungal melanomas are very aggressive tumors that readily metastasize to regional lymph nodes and the lungs. These forms are poorly responive to conventional therapies as chemo and radiation (Theon et al., 1997; Todoroff et al., 1997; Aronsohn et al., 1990). Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis in various organs and diseases. The formation of new blodd vessels represents a critical factor in the malignant growth of solid tumors and metastasis. VEGF plays an important role as pro-angiogenic and autocrine growth factor in several malignancies. In many cases neoplastic cells produce substantial amounts of VEGF and express VEGF receptors on their surfaces - thus utilizing VEGF as an autocrine growth stimulant (Clifford et al., 2001; Ferrara, 1992). Further,it has been shown that tumor cells protect themselves against therapeutic interventions such as chemotherapy or irradiation by the release of growth factors.
The objective of this study was to evaluate the influence of irradiation on VEGF and VEGF receptor (Flt-1, KDR) expression in the canine melanoma cell line TLM 1. Further aims were to determine radio-sensitivity of the cells and the role of radiation induced apoptosis.
This study showed that TLM 1 cells are radio-sensitive. Results also demonstrated that apoptosis is induced in a radiation dose dependent manner. VEGF was produced constitutively, with the main portion secret in the cell free supernatant. A significant up-regulation in the 8 and 10 Gy irradiated cells was visible. In addition, a minor portion of TLM 1 cells expressed VEGF-R 1 intracellularly, whereas no receptor was found on the cell surface. VEGFR-2 was detected in the cytoplasm and was down-regulated following radation with increasing dosages.