期刊
PATHOLOGY INTERNATIONAL
卷 72, 期 3, 页码 161-175出版社
WILEY
DOI: 10.1111/pin.13198
关键词
cancer-associated fibroblasts; immunoglobulin superfamily containing leucine-rich repeat; matrix remodeling-associated protein 8; Meflin; pancreatic cancer; tumor microenvironment
类别
资金
- Japan Agency for Medical Research and Development [20gm0810007h0105, 20gm1210009s0102]
- Japan Society for the Promotion of Science [18H02638, 20H03467]
- Grants-in-Aid for Scientific Research [18H02638, 20H03467] Funding Source: KAKEN
Recent studies have shown that cancer-associated fibroblasts (CAFs) are heterogeneous and can be categorized into cancer-promoting and -restraining CAFs. This study identifies MXRA8 as a new marker for CAFs, but the biological importance of MXRA8(+)CAF is still unclear.
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.
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