Ming Qi, Shuran Fan, Maohua Huang, Jinghua Pan, Yong Li, Qun Miao, Wenyu Lyu, Xiaobo Li, Lijuan Deng, Shenghui Qiu, Tongzheng Liu, Weiqing Deng, Xiaodong Chu, Chang Jiang, Wenzhuo He, Liangping Xia, Yunlong Yang, Jian Hong, Qi Qi, Wenqian Yin, Xiangning Liu, Changzheng Shi, Minfeng Chen, Wencai Ye, Dongmei Zhang
Vessel co-option has been demonstrated to mediate colorectal cancer liver metastasis (CRCLM) resistance to anti-angiogenic therapy. The current mechanisms underlying vessel co-option have mainly focused on the "hijacker" tumor cells, whereas the function of the "hijackee" sinusoidal blood vessels has not been explored. Here, we found that the occurrence of vessel co-option in bevacizumab-resistant CRCLM xenografts was associated with increased expression of fibroblast activation protein alpha (FAPα) in the co-opted hepatic stellate cells (HSCs), which was dramatically attenuated in HSC-specific conditional Fap-knockout mice bearing CRCLM allografts...
August 11, 2022: Journal of Clinical Investigation