α11β1 Integrin is Induced in a Subset of Cancer-Associated Fibroblasts in Desmoplastic Tumor Stroma and Mediates In Vitro Cell Migration

Cancers

Edna Cukierman¹  PugazendhiM. Erusappan²  Ning Lu²  Cédric Zeltz²  Hengshuo Liu²  Himalaya Parajuli²  Jahedul Alam²  Donald Gullberg²  Daniela-Elena Costea³  Anders Molven⁴  Heinz Hoschuetzky⁵ 

[1] Cancer Biology Department, Fox Chase Cancer Center, Temple Health, Philadelphia, PA 19111, USA;Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Jonas Lies vei 91, NO-5009 Bergen, Norway;Department of Pathology, Haukeland University Hospital, NO-5020 Bergen, Norway;Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, NO-5020 Bergen, Norway;nanoTools Antikörpertechnik, Tscheulinstr. 21, 79331 Teningen, Germany;

关键词: tumor microenvironment;    tumor stroma;    extracellular matrix;    fibrillar collagen;    cancer-associated fibroblasts;    integrin alpha11;   

DOI  :  10.3390/cancers11060765

来源: DOAJ

【 摘 要 】

Integrin α11β1 is a collagen receptor that has been reported to be overexpressed in the stroma of non-small cell lung cancer (NSCLC) and of head and neck squamous cell carcinoma (HNSCC). In the current study, we further analyzed integrin α11 expression in 14 tumor types by screening a tumor tissue array while using mAb 203E3, a newly developed monoclonal antibody to human α11. Different degrees of expression of integrin α11 were observed in the stroma of breast, ovary, skin, lung, uterus, stomach, and pancreatic ductal adenocarcinoma (PDAC) tumors. Co-expression queries with the myofibroblastic cancer-associated fibroblast (myCAF) marker, alpha smooth muscle actin (αSMA), demonstrated a moderate level of α11⁺ in myCAFs associated with PDAC and HNSCC tumors, and a lack of α11 expression in additional stromal cells (i.e., cells positive for fibroblast-specific protein 1 (FSP1) and NG2). The new function-blocking α11 antibody, mAb 203E1, inhibited cell adhesion to collagen I, partially hindered fibroblast-mediated collagen remodeling and obstructed the three-dimensional (3D) migration rates of PDAC myCAFs. Our data demonstrate that integrin α11 is expressed in a subset of non-pericyte-derived CAFs in a range of cancers and suggest that α11β1 constitutes an important receptor for collagen remodeling and CAF migration in the tumor microenvironment (TME).

【 授权许可】

Unknown