Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
J Dermatol Sci. 2010 Mar;57(3):149-54. doi: 10.1016/j.jdermsci.2009.12.008. Epub 2010 Jan 8.
CD147/basigin, a transmembrane protein belonging to the immunoglobulin super family, was originally cloned as a carrier of Lewis X carbohydrate antigen. CD147 is strongly related to cancer progression; it is highly expressed by various cancer cells including malignant melanoma (MM) cells and it plays important roles in tumor invasiveness, metastasis, cellular proliferation, and in vascular endothelial growth factor (VEGF) production, tumor cell glycolysis, and multi-drug resistance (MDR). CD147 on cancer cells induces matrix metalloproteinase expression by neighboring fibroblasts, leading to tumor cell invasion. In a nude mouse model of pulmonary metastasis from MM, the metastatic potential of CD147-expressing MM cells injected into the tail vein is abolished by CD147 silencing. CD147 enhances cellular proliferation and VEGF production by MM cells; it promotes tumor cell glycolysis by facilitating lactate transport in combination with monocarboxylate transporters, resulting in tumor progression. CD147 is responsible for the MDR phenotype via P-glycoprotein expression. These findings strongly suggest CD147 as a possible therapeutic target for overcoming metastasis and MDR, major obstacles to the effective treatment of malignant cancers.
CD147/基底膜糖蛋白，一种属于免疫球蛋白超家族的跨膜蛋白，最初被克隆为 Lewis X 碳水化合物抗原的载体。CD147 与癌症的进展密切相关；它在各种癌细胞中高度表达，包括恶性黑色素瘤 (MM) 细胞，并在肿瘤侵袭、转移、细胞增殖以及血管内皮生长因子 (VEGF) 产生、肿瘤细胞糖酵解和多药耐药 (MDR) 中发挥重要作用。癌细胞上的 CD147 通过邻近成纤维细胞诱导基质金属蛋白酶的表达，导致肿瘤细胞的侵袭。在 MM 肺转移的裸鼠模型中，通过沉默 CD147 可消除表达 CD147 的 MM 细胞注入尾静脉后的转移潜能。CD147 增强 MM 细胞的细胞增殖和 VEGF 产生；它通过与单羧酸转运蛋白结合促进乳酸的转运，从而促进肿瘤细胞糖酵解，导致肿瘤进展。CD147 通过 P-糖蛋白表达导致 MDR 表型。这些发现强烈表明 CD147 可能是克服转移和 MDR 的治疗靶点，这是有效治疗恶性癌症的主要障碍。
