Metastatic colorectal cancer cells upregulate SMLR1 that interacts with tumor-associated macrophages in the liver

Abstract

Colorectal cancer liver metastasis (CRLM) is the most common form of metastatic colorectal cancer (CRC), one of the leading causes of cancer deaths. The CRLM microenvironment tends to be more immunosuppressive, making immunotherapy less effective. By transcriptomics analysis, we discovered that small leucine-rich protein 1 (SMLR1) is upregulated in CRC liver metastases compared to primary tumors. High SMLR1 expression by the cancer is associated with poor prognosis. Proteomics analysis and cell retention assay revealed associations between SMLR1 and mannose receptor C-type 1 (MRC1, CD206) and sialic acid binding Ig-like lectin 1 (SIGLEC1, CD169) expressed on tumor-associated macrophages in the metastatic liver microenvironment. These data provide evidence that cancer cells modulate their metastatic niche via the upregulation of SMLR1 and physical interaction with immunosuppressive macrophages in the liver.