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

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

doi:10.3390/cancers11111766

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

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

Authors

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

Dr Wenbin Wei wenbin.wei2@durham.ac.uk
Chief Experimental Officer (Bioinformatics)

Ivy Chung

Paul G. Murray

Lee Fah Yap

Ian C. Paterson

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.

Citation

Lai, S. L., Tan, M. L., Hollows, R. J., Robinson, M., Ibrahim, M., Margielewska, S., …Paterson, I. C. (2019). Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1. Cancers, 11(11), https://doi.org/10.3390/cancers11111766

Journal Article Type	Article
Acceptance Date	Nov 5, 2019
Online Publication Date	Nov 9, 2019
Publication Date	Nov 30, 2019
Deposit Date	Nov 21, 2019
Publicly Available Date	Nov 22, 2019
Journal	Cancers
Publisher	MDPI
Peer Reviewed	Peer Reviewed
Volume	11
Issue	11
DOI	https://doi.org/10.3390/cancers11111766

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