Research on the role of Basigin (CD 147) in invasion and metastasis of malignant melanoma

Basigin（CD 147）被证明与成纤维细胞相互作用并刺激基质金属蛋白酶（MMPs）的表达，所述基质金属蛋白酶在肿瘤侵袭和转移中起重要作用。我们证明了表达basigin的人恶性黑色素瘤（MM）细胞与真皮成纤维细胞共培养导致成纤维细胞诱导MMP-1、MMP-2、MMP-3和MT 1-MMP的产生以及黑色素瘤细胞通过重建的基底膜的侵袭。besigin抗体抑制成纤维细胞MMPs的产生和黑色素瘤细胞的侵袭性。采用免疫组织化学方法检测18例无转移和10例有转移的MM患者的28例标本中basigin和MMPs的表达，以探讨basigin在MM转移中的作用。Basigin在黑色素瘤细胞中表达，但在成纤维细胞中不表达。与无转移的MM相比，有转移的MM具有显著更高的basigin表达。有转移的恶性黑色素瘤与无转移的恶性黑色素瘤细胞及成纤维细胞中MMPs的表达有显著性差异。成纤维细胞中基质金属蛋白酶的表达与basigin的表达水平呈正相关。这些免疫组化结果表明，基质金属蛋白酶可能表达在成纤维细胞以及黑色素瘤细胞伴随basigin，这是表达在黑色素瘤细胞更频繁的MM转移。Basigin在黑色素瘤细胞中高表达，可能通过刺激周围成纤维细胞表达MMPs在黑色素瘤细胞的侵袭和转移中发挥重要作用。

Basigin (CD147) was shown to interact with fibroblasts and stimulate expression of matrix metalloprotenases (MMPs) that play an important role in tumor invasiveness and metastasis. We demonstrated that coculture of basigin-expressiong human malignant melanoma (MM) cells with dermal fibroblasts resulted in the induction of MMP-1, MMP-2, MMP-3 and MT1-MMP production by fibroblasts and of melanoma cell invasion through a reconstituted basement membrane. Antibody to besigin inhibited both the production of MMPs by fibroblasts and the invasiveness of melanoma cells. Expression of basigin and MMPs in MM and surrounding fibroblasts was examined immunohistochemically in 28 specimens from 18 MM patients without metastasis and 10 with metastasis to investigate whether basigin plays a role in metastasis of MM in vivo. Basigin was expressed in melanoma cells but not in fibroblasts. MM with metastasis had significantly higher basigin expression compared to MM without metastasis. There were significant differences between MMs with and without metastasis in the expression of MMPs in both melanoma cells and fibroblasts. Expression of MMPs in fibroblasts was positively correlated with expression levels of basigin. These immunohistochemical findings indicate that MMPs might be expressed in fibroblasts as well as melanoma cells concomitantly with basigin, which was expressed in melanoma cells more frequently in MM with metastasis. Basigin is highly expressed in melanoma cells and may play an important role in their invasiveness and metastasis by stimulating surrounding fibroblasts to express MMPs.