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

Basigin （CD147）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，而MMPs在肿瘤侵袭和转移中起重要作用。我们证明，将表达盆蛋白的人恶性黑色素瘤（MM）细胞与真皮成纤维细胞共培养，可诱导成纤维细胞产生MMP-1、MMP-2、MMP-3和MT1-MMP，并诱导黑色素瘤细胞通过重组基底膜入侵。抗besigin抗体抑制成纤维细胞生成MMPs和黑色素瘤细胞的侵袭性。采用免疫组织化学方法检测了18例MM无转移和10例MM有转移的28例MM及周围成纤维细胞中basigin和MMPs的表达，探讨basigin是否在MM体内转移中起作用。Basigin在黑色素瘤细胞中表达，而在成纤维细胞中不表达。有转移的MM与无转移的MM相比，basigin的表达明显升高。在黑色素瘤细胞和成纤维细胞中，有和没有转移的MMPs在MMPs表达上有显著差异。成纤维细胞中MMPs的表达与basigin的表达水平呈正相关。这些免疫组织化学结果表明，MMPs可能在成纤维细胞和黑素瘤细胞中同时表达，而basigin在黑素瘤细胞中表达的频率更高。Basigin在黑色素瘤细胞中高度表达，可能通过刺激周围成纤维细胞表达MMPs，在黑色素瘤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.