Potential co-regulatory role of VEGF-A and VEGF-C in angiogenic event in thyroid cancer (#366)
Vascular endothelial growth factor (VEGF) promotes growth of blood or lymphatic vessels, termed angiogenesis and lymphangiogenesis. These share several basal mechanisms, including cross-talk between VEGF-A, C and their receptors, which may be important in the development of malignancies. Study aimed to identify relationships between VEGF-A, VEGF-C and their impact in angiogenesis and metastases in thyroid cancers.
We studied VEGF-A and VEGF-C mRNA expression in 123 thyroid cancers, 40 lymph node metastases and 7 non-malignant thyroid control tissues using qPCR. Protein expression for both VEGFs were determined by immunohistochemistry.
VEGF-A and VEGF-C mRNA over-expression was noted in 51% (n=62) and 27% (n=33) of the thyroid cancers respectively. VEGF-A and VEGF-C protein over-expression was also identified in 70% (n=86) and 62% (n=76) of the thyroid cancers. ANOVA showed significant expression differences for VEGF-A and VEGF-C in subtypes of thyroid carcinoma, lymph node metastasis and normal controls (P=1x10-6 and 1x10-5 respectively).
VEGF-A mRNA was significantly higher in cancers with lymph node metastases compared to non-metastatic cancers (p=0.001) however, most metastatic tumours under-expressed VEGF-C (p=0.0002). Similarly, VEGF-A protein expression was higher in metastases and VEGF-C protein was higher in non-metastatic lesions, though not significantly.
Finally, we used linear regression analysis to test previous proposals about physiological interactions of VEGF-A and VEGF-C expression. Our model indicated that in metastatic cancers, 32% of the expression of VEGF-A could be predicted by a positive influence of VEGF-C production (model p=0.0002).
These findings add weight to previous hypotheses concerning VEGF-A and C interaction. Early lymphangiogenic events were proposed to regulate angiogenesis, and changes to VEGF expression in this cancer population bear this out, with VEGF-C in early tumours giving way to VEGF-A in metastases. The commonality of local metastasis in thyroid cancer makes it a useful model to further examine mechanisms of angiogenesis and lymphangiogenesis in cancer metastasis.