Integrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?

Journal of Cell Communication and Signaling

article

Zeltz, Cédric¹  Navab, Roya²  Heljasvaara, Ritva³  Kusche-Gullberg, Marion¹  Lu, Ning¹  Tsao, Ming-Sound²  Gullberg, Donald¹ 

[1] Department of Biomedicine, Matrix Biology Group, Centre for Cancer Biomarkers, University of Bergen;Princess Margaret Cancer Center, University Health Network;Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu;Department of Laboratory Medicine and Pathobiology, University of Toronto

关键词: Tumor microenvironment;    Cancer-associated fibroblast;    Integrin;    Fibrosis;    Cancer therapy;   

DOI  :  10.1007/s12079-022-00673-3

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

There is currently an increased interest in understanding the role of the tumor microenvironment (TME) in tumor growth and progression. In this context the role of integrins in cancer-associated fibroblasts (CAFs) will need to be carefully re-evaluated. Fibroblast-derived cells are not only in the focus in tumors, but also in tissue fibrosis as well as in inflammatory conditions. The recent transcriptional profiling of what has been called “the pan-fibroblast cell lineage” in mouse and human tissues has identified novel transcriptional biomarker mRNAs encoding the secreted ECM proteins dermatopontin and collagen XV as well as the phosphatidylinositol-anchored membrane protein Pi16. Some of the genes identified in these fibroblasts scRNA-seq datasets will be useful for rigorous comparative characterizations of fibroblast-derived cell subpopulations. At the same time, it will be a challenge in the coming years to validate these transcriptional mRNA datasets at the protein-(expression) and at tissue-(distribution) levels and to find useful protein biomarker reagents that will facilitate fibroblast profiling at the cell level. In the current review we will focus on the role of the collagen-binding integrin α11β1 in CAFs, summarizing our own work as well as published datasets with information on α11 mRNA expression in selected tumors. Our experimental data suggest that α11β1 is more than just another biomarker and that it as a functional collagen receptor in the TME is playing a central role in regulating collagen assembly and matrix remodeling, which in turn impact tumor growth and metastasis.

【 授权许可】

CC BY