Matrix remodeling-associated protein 8 is a marker of a subset of cancer-associated fibroblasts in pancreatic cancer.
Matrix remodeling-associated protein 8 is a marker of a subset of cancer-associated fibroblasts in pancreatic cancer.
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基质重塑相关蛋白8是胰腺癌中癌症相关成纤维细胞亚群的标志。
DOI：
10.1111/pin.13198
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发表时间：
2022-03
影响因子：
2.2
通讯作者：
Enomoto, Atsushi
中科院分区：
文献类型：
--
作者：
Ichihara, Ryosuke;Shiraki, Yukihiro;Mizutani, Yasuyuki;Iida, Tadashi;Miyai, Yuki;Esaki, Nobutoshi;Kato, Akira;Mii, Shinji;Ando, Ryota;Hayashi, Masamichi;Takami, Hideki;Fujii, Tsutomu;Takahashi, Masahide;Enomoto, Atsushi
关键词：
癌症相关成纤维细胞(CAF)是肿瘤微环境的一个隔室，以前被认为是促进癌症进展的统一细胞群。然而，最近的研究表明，CAF是异质性的，至少存在两种类型的CAF，即促进癌症和抑制癌症的CAF。我们先前发现Meflin是胰腺导管腺癌(PDAC)中肿瘤抑制CAF(RCAF)的候选标记物。然而，由于缺乏对其全面基因签名的了解，rCAF的确切性质仍然难以捉摸。在这里，我们在人类癌症的单细胞转录分析中筛选其表达与Meflin相关的基因。在已鉴定的基因中，我们鉴定了基质重塑相关蛋白8(MXRA8)，它编码一种分子功能未知的I型跨膜蛋白。MXRA8在人PDAC样本中的表达分析表明，MXRA8与其他CAF标记存在差异共表达。此外，在PDAC患者或MXRA8基因敲除小鼠发生的同基因肿瘤中，MXRA8的表达不影响CAF在癌症进展中的作用，MXRA8+CAF的生物学重要性仍不清楚。总体而言，我们将MXRA8确定为一个新的CAF标记；需要进一步的研究来确定该标记的相关性。
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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