Correlation between the expression of thrombospondin-1 and neovascularization in mucoepidermoid carcinoma

Researchers have recently demonstrated that thrombospondin-1 (TSP-1) has an important function in regulating neovascularization. Whether it inhibits or accelerates neovascularization, however, is still controversial. We found few reports about the correlation between TSP-1 and vascularization in mucoepidermoid carcinoma. In this research, the distribution and expression of TSP-1 in mucoepidermoid carcinoma were investigated. We also analyzed (1) the correlation between the expression of TSP-1 and microvessel density (MVD), as an indicator of neovascularization activity, and (2) the effect of TSP-1 on neovascularization and tumor growth in the subcutaneous xenotransplanted model of mucoepidermoid carcinoma.

(1) The sites and intensity of expression of TSP-1 and the MVD were analyzed in 45 cases of mucoepidermoid carcinoma after surgery by the method of streptavidin-peroxidase (SP) immunohistochemistry; and (2) recombinant human thrombospondin-1 (rhTSP-1) was injected twice a week for five consecutive weeks around the tumor in the subcutaneous xenotransplanted tumor model of mucoepidermoid carcinoma in nude mice. Each week, the tumor size was measured, in order to draw the growth curve of the xenotransplanted tumor model of mucoepidermoid carcinoma, and MVD was measured.

(1) The positive expression of TSP-1 protein was 57.78% (26/45). Most positive staining for TSP-1 was found in the cytoplasm of the cancer cells, while some staining occurred in the extracellular matrix. The mean MVD in 45 cases of mucoepidermoid carcinoma was 58.17 +/- 19.77 per 100 visual fields. Tumors with a high expression of TSP-1 showed a low MVD value, and the TSP-1 immunocompetence and microvessel density showed a significant negative correlation (r(s) = -0.947, P < 0.001). (2) The xenotransplanted tumors with the injection doses of 1.25, 0.75 and 0.25 microg/ml respectively were 36.97%, 53.36% and 73.61% of the size of the control group ((451 +/- 92), (651 +/- 113), (898 +/- 86) and (1220 +/- 157) mm(3) respectively, F = 53.167, P < 0.001), and their weights were respectively 35.14%, 51.35% and 70.27% of the control group ((1.3 +/- 0.5), (1.9 +/- 0.5), (2.6 +/- 0.3), and (3.7 +/- 0.7) g respectively, F = 62.669, P < 0.001). Their MVDs were 25.00%, 45.93%, and 72.20% respectively of the control group and concentration dependent (15.43 +/- 3.45, 28.35 +/- 4.24, 44.57 +/- 3.35 and 61.73 +/- 5.43 per 100 visual fields respectively, F = 54.582, P < 0.001).

The TSP-1 has a higher expression in mucoepidermoid carcinoma and the expression has a significant negative correlation with neovascularization. The TSP-1 inhibits neovascularization and tumor growth, and it might be a new biological therapy for treatment of patients with mucoepidermoid carcinoma.