Expression of VEGF sub(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma

• Published in: British journal of cancer Vol. 97; no. 2; pp. 223 - 230
• Main Authors: Pritchard-Jones, RO, Dunn, DBA, Qiu, Y, Varey, AHR, Orlando, A, Rigby, H, Harper, S J, Bates, DO
• Format: Journal Article
• Language: English
• Published: 16.07.2007
• ISSN: 0007-0920
• DOI: 10.1038/sj.bjc.6603839

Malignant melanoma is the most lethal of the skin cancers and the UK incidence is rising faster than that of any other cancer. Angiogenesis - the growth of new vessels from preexisting vasculature - is an absolute requirement for tumour survival and progression beyond a few hundred microns in diameter. We previously described a class of anti-angiogenic isoforms of VEGF, VEGF sub(xxx)b, that inhibit tumour growth in animal models, and are downregulated in some cancers, but have not been investigated in melanoma To determine whether VEGF sub(xxx)b expression was altered in melanoma, PCR and immunohistochemistry of archived human tumour samples were used. In normal epidermis and in a proportion of melanoma samples, VEGF sub(xxx)b staining was seen. Some melanomas had much weaker staining. Subsequent examination revealed that expression was significantly reduced in primary melanoma samples (both horizontal and vertical growth phases) from patients who subsequently developed tumour metastasis compared with those who did not (analysis of variance (ANOVA) P<0.001 metastatic vs nonmetastatic), irrespective of tumour thickness, while the surrounding epidermis showed no difference in expression. Staining for total VEGF expression showed staining in metastatic and nonmetastatic melanomas, and normal epidermis. An absence of VEGF sub(xxx)b expression appears to predict metastatic spread in patients with primary melanoma These results suggest that there is a switch in splicing as part of the metastatic process, from anti-angiogenic to pro-angiogenic VEGF isoforms. This may form part of a wider metastatic splicing phenotype.