Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin/Islr in Cancer Fibrosis

Masahide Takahashi; Hiroki Kobayashi; Yasuyuki Mizutani; Akitoshi Hara; Tadashi Iida; Yuki Miyai; Naoya Asai; Atsushi Enomoto

doi:10.3389/fcell.2021.749924

Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin/Islr in Cancer Fibrosis

Front Cell Dev Biol. 2021 Oct 5:9:749924. doi: 10.3389/fcell.2021.749924. eCollection 2021.

Authors

Masahide Takahashi¹, Hiroki Kobayashi², Yasuyuki Mizutani³, Akitoshi Hara², Tadashi Iida³, Yuki Miyai², Naoya Asai⁴, Atsushi Enomoto²

Affiliations

¹ International Center for Cell and Gene Therapy, Fujita Health University, Toyoake, Japan.
² Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
³ Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴ Department of Pathology, Fujita Health University, Toyoake, Japan.

Abstract

Fibroblasts synthesise the extracellular matrix (ECM) such as collagen and elastin, the excessive accumulation of which can lead to fibrosis and organ dysfunction under pathological conditions. Cancer-associated fibroblasts (CAFs) are major constituents of the tumour microenvironment (TME) that accompany the desmoplastic reaction responsible for anti-cancer treatment resistance. Thus, it is important to dissect the roles of CAFs in the TME to develop new therapeutic strategies for refractory cancers. Recent progress in the studies of CAF biology suggests that the functions of CAFs are complicated and that they are composed of functionally distinct populations, including cancer-promoting CAFs (pCAFs) and cancer-restraining CAFs (rCAFs). We recently identified a new cell surface marker for rCAFs in pancreatic and colon cancers, designated as Meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue)/Islr (immunoglobulin super family containing leucine-rich repeat). Based on the distribution of Meflin/Islr-positive cells, we also considered it a specific candidate marker for mesenchymal stroma/stem cells. Meflin/Islr-positive CAFs have been shown to suppress cancer progression by being involved in regulating collagen structures and BMP signalling in the TME. This review describes the function of Meflin/Islr in cancer fibrosis as well as in cardiac and lung fibrosis and its potential in the development of new cancer therapeutics.

Keywords: Islr; Meflin; cancer-associated fibroblast; fibrosis; mesenchymal stromal/stem cell; tumour microenvironment.

Publication types

Review