Cancer Sci：抑制清道夫受体治疗肿瘤转移

清道夫受体（scavenger receptor）是吞噬细胞表面的一组异质性分子，至少以6种不同的分子形式存在。此类受体多见于巨噬细胞表面，它们以化学修饰的蛋白质、多核苷酸、多糖和磷脂等为配体并可促进其胞吞作用，起着清除体内有毒物质和衰老、凋亡或坏死细胞的作用。

清道夫受体成员5（SCARA5）是一类清道夫受体新成员，在人类肝细胞癌（HCC）中是一种新的候选肿瘤抑制基因。

近日刊登在Cancer Sci杂志上的一则研究发现各种癌症细胞系和肿瘤样本中，SCARA5表达都出现经常性地下调。此外，研究结果表明，在人类癌症细胞株SCARA5中，该受体上调导致肿瘤细胞的增殖、克隆形成能力急剧减少，迁移和体外侵袭能力也减弱。

此外，研究人员将荷瘤小鼠给予SCARA5-阳离子脂质体后，皮下人脑胶质瘤肿瘤的生长被抑制，同时自发性肺转移也被抑制。

而在另一个A549肺癌小鼠实验中，小鼠给予SCARA5-阳离子脂质体后A549肺转移也减少。与对照组相比，SCARA5治疗的U251老鼠自发性肺转移率减少77.3％，A549肺转移率减少70.2％。

为了探索的分子机制，研究者采用免疫印迹方法，结果表明SCARA5能与FAK相互作用发挥作用。有趣的是SCARA5的上调对STAT3以及一些下游信号包括cyclinB1、cyclinD1、AKT、MMP-9和VEGF-A的失活是必须的。总的来说，这些研究结果首次证实了SCARA5可能是一个有前途的抗肿瘤转移的癌基因治疗新靶标。

doi:10.1111/j.1349-7006.2012.02350.x
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Therapeutic upregulation of SCARA5 inhibits tumor growth and metastasis.

Yan N, Zhang S, Yang Y, Cheng L, Li C, Dai L, Dai L, Zhang X, Fan P, Tian H, Wang R, Chen X, Su X, Li Y, Zhang J, Du T, Wei Y, Deng H.

Class A scavenger receptor member 5 (SCARA5) is a new member of class A scavenger receptor, which serves as a novel candidate tumor suppressor gene in human hepatocellular carcinoma (HCC) in recent report. Here, we found that SCARA5 expression was frequently downregulated in various cancer cell lines and tumor samples. Additionally, our results showed that upexpression SCARA5 in human cancer cell line led to dramatically decreased cell proliferation, clone formation, migration and invasion in vitro. Furthermore, our study showed that systemic treatment of tumor-bearing mice with SCARA5-Cationic Liposome Complex not only reduced the subcutaneous human glioma tumor growth but also markedly suppressed formation of spontaneous lung metastases. We found similar results in another experiment using mice bearing experimental A549 lung metastasis. Compared with the untreated control group, the mice treated with SCARA5 exhibited a reduction U251 spontaneous lung metastasis rate of 77.3% and experimental A549 lung metastasis rate of 70.2%, respectively. To explore the molecular mechanisms, western blot was done and the results showed that SCARA5 physically associated with FAK. Interestingly, upregulation of SCARA5 was capable for inactivation of STAT3 and some downstream signaling including cyclinB1, cyclinD1, AKT, surviving, MMP-9 and VEGF-A. Overall, these findings provided the first evidence that SCARA5 might be a promising target for the development of new anti-metastasis reagent for cancer gene therapy.