索拉非尼
转移
医学
肝细胞癌
癌症研究
肺
吡非尼酮
肺癌
内科学
肿瘤科
癌症
特发性肺纤维化
作者
Mingyu Liu,Lulu Xie,Yuying Zhang,Jianning Chen,Xiang Zhang,Ye Chen,Wensou Huang,Mingyue Cai,Licong Liang,Miaoling Lai,Jingjun Huang,Yongjian Guo,Liteng Lin,Kangshun Zhu
标识
DOI:10.1038/s41419-023-05550-4
摘要
Abstract Hepatocellular carcinoma (HCC) with lung metastasis is associated with poor prognosis and poor therapeutic outcomes. Studies have demonstrated that stiffened stroma can promote metastasis in various tumors. However, how the lung mechanical microenvironment favors circulating tumor cells remains unclear in metastatic HCC. Here, we found that the expression of cell migration-inducing hyaluronan-binding protein (CEMIP) was closely associated with lung metastasis and can promote pre-metastatic niche formation by increasing lung matrix stiffness. Furthermore, upregulated serum CEMIP was indicative of lung fibrotic changes severity in patients with HCC lung metastasis. By directly targeting CEMIP, pirfenidone can inhibit CEMIP/TGF-β1/Smad signaling pathway and reduce lung metastases stiffening, demonstrating promising antitumor activity. Pirfenidone in combination with sorafenib can more effectively suppress the incidence of lung metastasis compared with sorafenib alone. This study is the first attempt to modulate the mechanical microenvironment for HCC therapy and highlights CEMIP as a potential target for the prevention and treatment of HCC lung metastasis.
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