Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1

Sook Ling Lai; May Leng Tan; Robert J Hollows; Max Robinson; Maha Ibrahim; Sandra Margielewska; E Kenneth Parkinson; Anand Ramanathan; Rosnah Binti Zain; Hisham Mehanna; Rachel J Spruce; Wenbin Wei; Ivy Chung; Paul G Murray; Lee Fah Yap; Ian C Paterson

doi:10.3390/cancers11111766

Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1

Cancers (Basel). 2019 Nov 9;11(11):1766. doi: 10.3390/cancers11111766.

Authors

Sook Ling Lai¹, May Leng Tan¹, Robert J Hollows², Max Robinson³, Maha Ibrahim^{2

4}, Sandra Margielewska², E Kenneth Parkinson⁵, Anand Ramanathan^{6

7}, Rosnah Binti Zain^{7

8}, Hisham Mehanna^{9

10}, Rachel J Spruce^{9

10}, Wenbin Wei^{2

11}, Ivy Chung¹², Paul G Murray^{2

13}, Lee Fah Yap¹, Ian C Paterson¹

Affiliations

¹ Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia.
² Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
³ Centre for Oral Health Research, Newcastle University, Newcastle NE2 4BW, UK.
⁴ South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt.
⁵ Centre for Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK.
⁶ Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia.
⁷ Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia.
⁸ Faculty of Dentistry, MAHSA University, Bandar Saujana Putra 42610, Malaysia.
⁹ Institute of Head and Neck Studies and Education (InHANSE), University of Birmingham, Birmingham B15 2TT, UK.
¹⁰ Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK.
¹¹ Department of Biosciences, Durham University, Durham DH1 3LE, UK.
¹² Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
¹³ Health Research Institute, University of Limerick, Limerick V94 T9PX, Ireland.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.

Keywords: DDR1; collagen; head and neck cancer.

Abstract

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