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

• Main Authors: Cédric Zeltz, Jahedul Alam, Hengshuo Liu, Pugazendhi M. Erusappan, Heinz Hoschuetzky, Anders Molven, Himalaya Parajuli, Edna Cukierman, Daniela-Elena Costea, Ning Lu, Donald Gullberg
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: Cancers
• Subjects: tumor microenvironment; tumor stroma; extracellular matrix; fibrillar collagen; cancer-associated fibroblasts; integrin alpha11
• Online Access: https://www.mdpi.com/2072-6694/11/6/765

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).