Colorectal cancer cells promote osteoclastogenesis and bone destruction through regulating EGF/ERK/CCL3 pathway

作者：Gong Zi-chen, Qian Jin, Zhang Yi-na, Wei Wang, Xia Kang, Wei Xu, Juan Wu, Zheng Wei · 发表于：Bioscience Reports · 年份：2020 · DOI：10.1042/bsr20201175 · 被引用次数：12 · 研究领域：Bone Metabolism and Diseases、Bone health and treatments、Bone and Dental Protein Studies

Bone metastasis of colorectal cancer (CRC) cells leads to osteolysis. Aberrant activation of osteoclasts is responsible for bone resorption in tumor. In general, bone marrow-derived monocytes (BMMs) differentiate into osteoclasts, however, how CRC cells interact with BMMs and how to regulate the differentiation is elusive. We here report that CRC cells promote bone resorption in bone metastasis. Transcriptomic profiling revealed CCL3 up-regulated in MC-38 conditional medium treated BMMs. Further investigation demonstrated that CCL3 produced by BMMs facilitated cell infusion and thus promoted the osteoclastogenesis. In addition, CRC cells derived EGF stimulated the production of CCL3 in BMMs through activation of ERK/CREB pathway. Blockage of EGF or CCL3 can efficiently attenuate the osteolysis in bone metastasis of CRC.