HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma
HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma
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DOI：
10.1158/1541-7786.mcr-06-0286
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发表时间：
2007-06-01
影响因子：
5.2
通讯作者：
Chen, Zhi-Nan
中科院分区：
文献类型：
--
作者：
Xu, Jing;Xu, Hui-Yun;Chen, Zhi-Nan
CD 147分子被报道与某些癌症的恶性程度相关，然而，它是否参与肝细胞癌（HCC）的进展仍不清楚。本研究旨在探讨CD 147家族成员HAb 18 G/CD 147及其抗体HAb 18和LICARTIN在肝癌侵袭和转移中的作用。我们观察到HAb 18 G/CD 147基因沉默可显著降低肝癌细胞基质金属蛋白酶（MMP）的分泌和侵袭能力（P < 0.001）。肝癌细胞MMP沉默也能显著抑制与成纤维细胞共培养的e细胞的侵袭，但其抑制作用明显弱于肝癌细胞HAb 18 G/CD 147沉默和成纤维细胞MMP沉默（P < 0.001）。用HAb 18单克隆抗体阻断HCC细胞表面的HAb 18 G/CD 147分子，对MMP分泌和细胞侵袭能力也有类似的抑制作用，但对细胞生长无明显影响。(131)I-HAb 18F（ab '）（2）（LICARTIN）对肝癌细胞的生长有明显的抑制作用（P < 0.001）。在裸鼠原位肝癌模型中，HAb 18和利卡汀治疗有效地减少了肿瘤的生长和转移以及癌旁组织中HCC微环境中三种主要因子（MMPS、血管内皮生长因子和成纤维细胞表面蛋白）的表达。总之，这些结果表明HAb 18 G/CD 147主要通过调节成纤维细胞以及HCC细胞本身来破坏HCC微环境，在HCC侵袭和转移中起重要作用。利卡汀可作为靶向HAb 18 G/CD 147的药物用于肝癌的抗转移和复发治疗。
CD147 molecule is reported to be correlated with the malignancy of some cancers; however, it remains unclear whether it is involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the function of HAb18G/CD147, a member of CD147 family, and its antibodies, HAb18 and LICARTIN, in HCC invasion and metastasis. We observed that HAb1 8G/CD1 47 gene silence in HCC cells significantly decreased the secretion of matrix metal loprotei nase (MMP) and the invasive potential of HCC cells (P < 0.001). MMP silence in HCC cells also significantly suppressed the invasion o of the e cells when cocultured with fibroblasts; however, its inhibitory effect was significantly weaker than that of both HAb18G/CD147 silence in HCC cells and that of MMP silence in fibroblasts (P < 0.001). Blocking the HAb18G/CD147 molecule on HCC cells with HAb18 monoclonal antibody resulted in a similar suppressive effect on MMP secretion and cell invasion, but with no significant effects on the cell growth. (131) I-labeled HAb18 F(ab ')(2) (LICARTIN), however, significantly inhibited the in vitro growth of HCC cells (P < 0.001). In an orthotopic model of HCC in nude mice, HAb18 and LICARTIN treatment effectively reduced the tumor growth and metastasis as well as the expression of three major factors in the HCC microenviroment (MMPS, vascular endothelial growth factor, and fibroblast surface protein) in the paracancer tissues. Overall, these results suggest that HAb18G/CD147 plays an important role in HCC invasion and metastasis mainly via modulating fibroblasts, as well as HCC cells themselves to disrupt the HCC microenviroment. LICARTIN can be used as a drug targeting to HAb18G/CD147 in antimetastasis and recurrence therapy of HCC.