Matrix remodeling‐associated protein 8 is a marker of a subset of cancer‐associated fibroblasts in pancreatic cancer

Cancer‐associated fibroblasts (CAFs), a compartment of the tumor microenvironment, were previously thought to be a uniform cell population that promotes cancer progression. However, recent studies have shown that CAFs are heterogeneous and that there are at least two types of CAFs, that is, cancer‐promoting and ‐restraining CAFs. We previously identified Meflin as a candidate marker of cancer‐restraining CAFs (rCAFs) in pancreatic ductal adenocarcinoma (PDAC). The precise nature of rCAFs, however, has remained elusive owing to a lack of understanding of their comprehensive gene signatures. Here, we screened genes whose expression correlated with Meflin in single‐cell transcriptomic analyses of human cancers. Among the identified genes, we identified matrix remodeling‐associated protein 8 (MXRA8), which encodes a type I transmembrane protein with unknown molecular function. Analysis of MXRA8 expression in human PDAC samples showed that MXRA8 was differentially co‐expressed with other CAF markers. Moreover, in patients with PDAC or syngeneic tumors developed in MXRA8‐knockout mice, MXRA8 expression did not affect the roles of CAFs in cancer progression, and the biological importance of MXRA8 (+) CAFs is still unclear. Overall, we identified MXRA8 as a new CAF marker; further studies are needed to determine the relevance of this marker.