1. Department of Radiation Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710086, China
2. Xi'an Medical University, Xi'an, 710086, China
Background: Since metastasis is the primary cause of death in human colorectal cancer (CRC) patients, the exact mechanism underlying CRC metastasis remains unclear. Here, we provide evidence for a unique function of HomeoboxC10 (HOXC10) in driving CRC metastasis, as well as treatment options for these subpopulation patients.
Methods: Immunohistochemistry detected the expression of HOXC10 in the human CRC cohort. The function of HOXC10 in CRC metastasis was investigated using the cecum orthotopic model.
Results: In CRC patients, elevated expression of HOXC10 expression was linked to lymph node metastases, distant metastasis, worse tumor differentiation, higher AJCC stage, and poor prognosis. HOXC10 is also an independent predictive predictor for CRC patients (P<0.001). HOXC10 overexpression increased the metastasis ability of MC38 cells and promoted the infiltration of MDSCs by upregulating CXCL5 at the same time. The CXCR2 inhibitor can reduce the rate of metastasis in MC38 cells by reducing MDSCs infiltration. SB225002, a CXCR2 inhibitor, and anti-programmed death-ligand 1 (anti-PD-L1) can significantly prevent CRC metastasis.
Conclusions: HOXC10 overexpression upregulated CXCL5, which promoted MDSCs infiltration. Interrupting this loop might be a potential therapy option for HOXC10-induced CRC metastasis.
Keywords: colorectal cancer, HOXC10, myeloid-derived suppressor cells.