TY - JOUR
T1 - Matrix remodeling-associated protein 8 is a marker of a subset of cancer-associated fibroblasts in pancreatic cancer
AU - Ichihara, Ryosuke
AU - Shiraki, Yukihiro
AU - Mizutani, Yasuyuki
AU - Iida, Tadashi
AU - Miyai, Yuki
AU - Esaki, Nobutoshi
AU - Kato, Akira
AU - Mii, Shinji
AU - Ando, Ryota
AU - Hayashi, Masamichi
AU - Takami, Hideki
AU - Fujii, Tsutomu
AU - Takahashi, Masahide
AU - Enomoto, Atsushi
N1 - Funding Information:
We thank David Tuveson (Cold Spring Harbor Laboratory) and Chang‐il Hwang (UC Davis College of Biological Sciences) for providing the mouse PDAC cell lines mT5 and Kozo Uchiyama (Nagoya University) for technical assistance. This work was supported by a Grant‐in‐Aid for Scientific Research (B) (Grant Nos. 18H02638 to Atsushi Enomoto and 20H03467 to Masahide Takahashi) commissioned by the Ministry of Education, Culture, Sports, Science and Technology of Japan; Nagoya University Hospital Funding for Clinical Research (to Atsushi Enomoto); AMED‐CREST (Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology; Grant Nos. 20gm0810007h0105 and 20gm1210009s0102 to Atsushi Enomoto).
Publisher Copyright:
© 2022 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122757094&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122757094&partnerID=8YFLogxK
U2 - 10.1111/pin.13198
DO - 10.1111/pin.13198
M3 - Article
C2 - 35020975
AN - SCOPUS:85122757094
SN - 1320-5463
VL - 72
SP - 161
EP - 175
JO - Acta Pathologica Japonica
JF - Acta Pathologica Japonica
IS - 3
ER -