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- Title
α11β1 Integrin is Induced in a Subset of Cancer-Associated Fibroblasts in Desmoplastic Tumor Stroma and Mediates In Vitro Cell Migration.
- Authors
Zeltz, Cédric; Alam, Jahedul; Liu, Hengshuo; Erusappan, Pugazendhi M.; Hoschuetzky, Heinz; Molven, Anders; Parajuli, Himalaya; Cukierman, Edna; Costea, Daniela-Elena; Lu, Ning; Gullberg, Donald
- Abstract
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).
- Subjects
BREAST tumor diagnosis; CANCER diagnosis; CANCER genetics; MELANOMA diagnosis; ADENOCARCINOMA; ANIMAL experimentation; CELL adhesion molecules; CELL motility; COLLAGEN; FIBROBLASTS; GENE expression; IMMUNOGLOBULINS; LUNG tumors; MICE; MONOCLONAL antibodies; MUSCLE cells; MUSCLE proteins; OVARIAN tumors; PANCREATIC tumors; SKIN tumors; STOMACH tumors; UTERINE tumors; DUCTAL carcinoma; IN vitro studies; IMMUNOLOGIC receptors
- Publication
Cancers, 2019, Vol 11, Issue 6, p765
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11060765