α11β1 Integrin is Induced in a Subset of Cancer-Associated Fibroblasts in Desmoplastic Tumor Stroma and Mediates In Vitro Cell Migration
by
Cédric Zeltz 1, Jahedul Alam 1, Hengshuo Liu 1, Pugazendhi M. Erusappan 1, Heinz Hoschuetzky 2, Anders Molven 3,4
, Himalaya Parajuli 1, Edna Cukierman 5, Daniela-Elena Costea 4,6, Ning Lu 1 and Donald Gullberg 1,*
, Himalaya Parajuli 1, Edna Cukierman 5, Daniela-Elena Costea 4,6, Ning Lu 1 and Donald Gullberg 1,*
1
Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Jonas Lies vei 91, NO-5009 Bergen, Norway
2
nanoTools Antikörpertechnik, Tscheulinstr. 21, 79331 Teningen, Germany
3
Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, NO-5020 Bergen, Norway
4
Department of Pathology, Haukeland University Hospital, NO-5020 Bergen, Norway
5
Cancer Biology Department, Fox Chase Cancer Center, Temple Health, Philadelphia, PA 19111, USA
6
Department of Clinical Medicine, Center for Cancer Biomarkers CCBIO and Gade Laboratory for Pathology, University of Bergen, NO-5020 Bergen, Norway
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 765; https://doi.org/10.3390/cancers11060765
Received: 13 April 2019 / Revised: 26 May 2019 / Accepted: 29 May 2019 / Published: 1 June 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
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).
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Keywords:
tumor microenvironment; tumor stroma; extracellular matrix; fibrillar collagen; cancer-associated fibroblasts; integrin alpha11
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MDPI and ACS Style
Zeltz, C.; Alam, J.; Liu, H.; Erusappan, P.M.; Hoschuetzky, H.; Molven, A.; Parajuli, H.; Cukierman, E.; Costea, D.-E.; Lu, N.; Gullberg, D. α11β1 Integrin is Induced in a Subset of Cancer-Associated Fibroblasts in Desmoplastic Tumor Stroma and Mediates In Vitro Cell Migration. Cancers 2019, 11, 765.
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