APOC1 expressed in macrophages promotes the pulmonary metastasis of colorectal cancer via CCL2/CCL5.

Metastasis is the main cause of death in colorectal cancer (CRC), and the lungs are common sites of metastasis. However, there is little effective target to intervene colorectal cancer pulmonary metastasis (CCPM), especially on its unique immune microenvironment. In this study, sixteen genes were identified as core CCPM-related differentially expressed genes (DEGs) between CRC and CCPM. Three genes including Apolipoprotein C1 (APOC1) were associated with prognosis, stage and metastasis of CRC. In immunohistochemistry, APOC1 was mainly expressed in macrophages, and expressed more in CCPM than CRC. Patients with synchronous CCPM, higher stage, poorer OS and CCPM-free interval tended to have higher expression. In experiments in vitro, knockdown of APOC1 in macrophages reduced the migration, invasion, and epithelial-mesenchymal transition of CRC cells. Knockdown of APOC1 in macrophages significantly decreased secretion of chemokines like CCL2 and CCL5. The pro-metastatic effect of macrophages expressing APOC1 was partially blocked by the antibodies of CCL2 and CCL5. Activation of STAT3 was a key process in APOC1's regulation of CCL2 and CCL5. In experiments in vivo, knockdown of APOC1 in macrophages reduced pulmonary metastasis. To conclude, APOC1 is one of core CCPM-related DEGs and associated with the metastasis and survival of CRC. Macrophages expressing APOC1 promote the CCPM by APOC1-STAT3-CCL2/CCL5 axis. APOC1 and macrophages expressing APOC1 play vital roles and may be potential therapeutic targets in CCPM.