Zeltz Cédric, Navab Roya, Heljasvaara Ritva, Kusche-Gullberg Marion, Lu Ning, Tsao Ming-Sound, Gullberg Donald
Department of Biomedicine, Matrix Biology Group, Centre for Cancer Biomarkers, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway.
Princess Margaret Cancer Center, University Health Network, Toronto, ON, M5G 1L7, Canada.
J Cell Commun Signal. 2022 Dec;16(4):649-660. doi: 10.1007/s12079-022-00673-3. Epub 2022 Apr 4.
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.
目前，人们对了解肿瘤微环境（TME）在肿瘤生长和进展中的作用兴趣日增。在此背景下，整合素在癌症相关成纤维细胞（CAFs）中的作用需要仔细重新评估。成纤维细胞衍生的细胞不仅是肿瘤研究的焦点，在组织纤维化以及炎症状态中也是如此。最近对小鼠和人类组织中所谓“泛成纤维细胞谱系”的转录谱分析，确定了编码分泌型细胞外基质蛋白皮肤桥蛋白和胶原蛋白XV以及磷脂酰肌醇锚定膜蛋白Pi16的新型转录生物标志物mRNA。在这些成纤维细胞的单细胞RNA测序数据集中鉴定出的一些基因，将有助于对成纤维细胞衍生的细胞亚群进行严格的比较表征。与此同时，在未来几年，在蛋白质（表达）和组织（分布）水平验证这些转录mRNA数据集，并找到有助于在细胞水平进行成纤维细胞分析的有用蛋白质生物标志物试剂，将是一项挑战。在当前的综述中，我们将重点关注胶原结合整合素α11β1在CAFs中的作用，总结我们自己的工作以及已发表的数据集中有关α11 mRNA在选定肿瘤中表达的信息。我们的实验数据表明，α11β1不仅仅是另一种生物标志物，而且作为TME中的一种功能性胶原受体，它在调节胶原组装和基质重塑中发挥着核心作用，进而影响肿瘤生长和转移。
