基质金属蛋白酶7在恶性黑素瘤中的表达

Expression of matrix metalloproteinase 7 in malignant melanoma

目的探讨基质金属蛋白酶7（MMP7）的表达与恶性黑素瘤浸润、转移的关系。方法采用免疫组化SP法研究MMP7在恶性黑素瘤（30例）、交界痣（30例）、正常人皮肤（15例）组织中的表达，并观察其在恶性黑素瘤A375细胞株和不同浓度乙酰肝素酶反义寡核苷酸转染的裸鼠体内恶性黑素瘤移植瘤中的表达情况。结果MMP7在恶性黑素瘤组、交界痣组及正常人皮肤组中的阳性表达率分别为83．33％（25／30）、6．67％（2／30）和0，恶性黑素瘤组与交界痣组MMP7的阳性表达率比较，X^2=35．62，P〈0．01；交界痣组与正常人皮肤组比较，差异无统计学意义。10、20、30umol／L乙酰肝素酶反义寡核苷酸对裸鼠体内恶性黑素瘤移植瘤MMP7表达表现出不同程度的抑制作用，30Ixmol／L组的抑制作用最强，与其他2个组相比，差异均有统计学意义（P〈0．05）。MMP7在A375细胞株中呈强阳性表达。结论MMP7在恶性黑素瘤中的表达明显高于其在交界痣和正常人皮肤；乙酰肝素酶反义寡核苷酸对裸鼠体内恶性黑素瘤移植瘤中MMP7的表达有显著抑制效应；MMP7在A375细胞株中呈强阳性表达。

Objective To study the relationship of matrix metalloproteinase 7 （MMP7） expression to the infiltration and metastasis of malignant melanoma. Methods Various concentrations （ 10, 20, 30 umol/L） of heparanase antisense oligodeoxynucleotide （ASODN） was used to transfect human malignant melanoma cell line A375. Then, the transfected cells were subcutaneously inoculated into the right back of nude mice. Six weeks after the inoculation, transplanted tumors were isolated from the mice, and the levels of MMP7 protein expression were assessed by SP immunohistochemistry. The expression rate of MMP7 was also examined by SP immunohistochemistry in A375 cells and in tissue samples from patients with malignant melanoma （n = 30）, junctional nevus （n = 30） and normal human controls （n = 15）. Results The expression rate of MMP-7 was 83.33% （25/30）, 6.67% （2/30） and 0 （0/15） respectively in malignant melanoma, junctional nevus and normal skin tissue samples; there was a significant difference in the positivity rate of MMP-7 between the malignant melanoma group and junctional nevus group （X^2= 35.62, P = 0.000） as well as normal control group （X^2 = 28.12, P= 0.000）, but not between the junctional nevus group and normal control group （P〉 0.05）. The expression of MMP-7 in transplanted tumor was decreased to a varying degreee by three levels of ASODN, and the inhibitory effects of 30 mol/L ASODN were the strongest （P 〈 0.05）. MMP-7 protein was also highly expressed in A375 cells. Conclusions The expression of MMP-7 in cutaneous malignant melanoma is higher than that in junctional nevus and normal skin tissue. Hpa-ASODN significantly inhibits the expression of MMP-7 in transplanted tumors in nude mice. MMP-7 is highly expressed in A375 cells.