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Zeltz C , Alam J , Liu H , Erusappan PM , Hoschuetzky H , Molven A , Parajuli H , Cukierman E , Costea DE , Lu N , Gullberg D
alpha11beta1 Integrin is Induced in a Subset of Cancer-Associated Fibroblasts in Desmoplastic Tumor Stroma and Mediates In Vitro Cell Migration
Cancers (Basel). 2019 Jun 1;11(6)
PMID: 31159419    PMCID: PMC6627481    URL: https://www.ncbi.nlm.nih.gov/pubmed/31159419
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Abstract
Integrin alpha11beta1 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 alpha11 expression in 14 tumor types by screening a tumor tissue array while using mAb 203E3, a newly developed monoclonal antibody to human alpha11. Different degrees of expression of integrin alpha11 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 (alphaSMA), demonstrated a moderate level of alpha11(+) in myCAFs associated with PDAC and HNSCC tumors, and a lack of alpha11 expression in additional stromal cells (i.e., cells positive for fibroblast-specific protein 1 (FSP1) and NG2). The new function-blocking alpha11 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 alpha11 is expressed in a subset of non-pericyte-derived CAFs in a range of cancers and suggest that alpha11beta1 constitutes an important receptor for collagen remodeling and CAF migration in the tumor microenvironment (TME).
Notes
Zeltz, Cedric Alam, Jahedul Liu, Hengshuo Erusappan, Pugazendhi M Hoschuetzky, Heinz Molven, Anders Parajuli, Himalaya Cukierman, Edna Costea, Daniela-Elena Lu, Ning Gullberg, Donald ID 223250/Norwegian Centre of Excellence grant Research Council of Norway ID 197066/EEA grant Poland Norway MOMENTO ID 911899/Western Norway Regional Health Authority R01CA232256 (EC), R21CA231252 (EC)/NIH/NCI grants CA06927/NIH/NCI grants 316610/People Programme (Marie Curie Actions) of the European Union s Seventh Framework Programme FP7/2007-2013/ Journal Article Switzerland Cancers (Basel). 2019 Jun 1;11(6). pii: cancers11060765. doi: 10.3390/cancers11060765.