doi:10.1111/j.1349-7006.2012.02350.x
PMC:
PMID:
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.
来源:生物谷