肝癌细胞诱导微环境中肝星状细胞（HSCs）活化，活化的HSCs又反作用于肝癌细胞，两者双向作用形成一个促癌环路，但其具体的分子机制尚未阐明。课题组前期研究发现肝癌细胞分泌的SULF2可水解HSPGs的6-O位硫酸基团，使储存在HSPGs上的生长因子解离，从而提高局部的生长因子浓度，发挥促癌作用。细胞外基质及细胞膜表面的HSPGs储存有大量PDGF，其可有效刺激HSCs活化，以PDGF-B/C两种亚型作用最为强烈。故本课题拟通过免疫组化，免疫荧光，质谱分析，ELISA结合分析法，细胞共培养，基因表达检测，裸鼠及SULF2转基因小鼠肝癌模型等方法验证如下科学假说：肝癌细胞高表达的SULF2通过增加PDGF-B/C释放，一方面刺激微环境中HSCs活化、增殖，提高HSCs分泌癌相关细胞外基质及生长因子的水平；另一方面直接激活肝癌细胞的PDGF受体及下游信号通路，而发挥促癌作用。

HCC cells can induce activation of HSCs during carcinogenesis, while activated HSCs promote HCC cells growth and migration. Bidirectional interactions between HCC cells and HSCs may function as an "amplification loop" to further enhance tumor progression，however the underlying mechanism still need to be elucidated. Our previous studies have showed that SULF2 secreted by HCC cells, which removes the 6-O-sulfate groups from HSPGs, releases growth factors from sequestration sites on HSPGs. Thus may increase the local concentration of growth factors and enhance tumor progression. Plenty of PDGF is sequestrated on HSPGs of cell memberane or extracellular matrixs, which can dramaticlly activate HSCs, wherein PDGF-B/C are the two most potent isoforms. Thus we hypothesize that high expression of SULF2 in HCC cells by releasing PDGF-B/C, enhances the activation and proliferation of HSCs thereby increaseing the levels of cancer-associated ECMs and growth factors on one hand, on the other hand directly promotes HCC progression through activating PDGF and the downstream signalings. We plan to test the hypothesis by using immunohistochemical staining, immunofluorescence staining, cell co-culture, ELISA binding assay, nude mice and SULF2 Transgenic mice models.