The Research Of Vasculogenic Mimicry In Melanoma

Objective: To investigate vasculogenic mimicry in melanomas and explore whether the tumor cells come into being vasculogenic mimicry by self- metamorphose in order to acquire blood supply to sustain growth. At the same time the molecular mechanism and clinical significance of vasculogenic mimicry was investigated in this study.Methods: First 60 cases of melanoma were enrolled in our study and made into tissue microarray . Subsequently we stained repeatly these tissue microarray sections for CD31 and PAS and compared the area of positive by gridding-count. These tumors were divided into mimicry group and non-mimicry group according to the outcome of PAS and compare difference of the staining outcome between the two groups. VEGF,COX-2, TIMP-2,MMP-2,ICAM were immunohistochemically stained in tissue microarray sections in order to illustrate molecular mechanism of vasculogenic mimicry. After vasculogenic mimicry existing in melanomas was proved from ultrastructure level. Furthermore We also constructed tri-dimension culture model of malignant melanoma cell line. At last the mice of C57 was innoculated with the malignant melanoma B16 to were investigated if a implant tumor has vasculogenic mimicry or not.Results There is a significant difference of CD31 and PAS in melanomas(P<0.01). The number of vasculogenic mimicry in melanomas whose malignant are low-grade is less than its tumors whose malignant are high-grade. These patients had a badly prognosis when vasculogenic mimicry existed in the tumors. The expression of VEGF, COX -2 in malignant melanoma that exist vasculogenic mimicry is lower than its in tumors that are in absence of vasculogenic mimicry, but the expression ofVEGF, COX -2 in high-grade malignant tumors is higher than its expression in low-grade malignant tumors. The positive degree of VEGF is correlated with the expression of COX-2. we also found that the tumor cells can express CD31, PAS, TIMP-2,MMP-2,ICAM. Research with electron microscope proved tumor cells constitute the wall of vasculogenic mimicry. Tri-dimension culture model of malignant melanoma cell line also testified the tumor cells self-metamorphose and vasculorized trend. Animal experiment proved that vasculogenic mimicry can exist in the implant tumors.Conclusion: Vasculogenic mimicry exists in melanomas. The tumor cells can imitate the vessels structure and constitute a channel system which can convey blood by self-metamorphose and the interaction with extra cell matrix. The tumor cells acquired blood supply to sustain growth and metastasis by this manner and lead to a badly prognosis . The difference and their relation between the VEGF and COX-2 expression prove that some malignant melanoma possess unique mole-mechanism of tumor metastasis and blood supply. TIMP, MMP-2,1C AM were secreted by the tumor cells can boost the adhere of tumor cells and matrix remold and turn into the substance base of vasculogenic mimicry . Some anti-vessel theraphy in high malignant tumors cann't reach a good curative effect may be relative with different micro-circulative pattern.