Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1
Abstract
:1. Introduction
2. Results
2.1. Collagen Expression in CAFs and HNSCCs
2.2. DDR1 Is Over-Expressed in HNSCCs
2.3. Collagen Stimulates Proliferation and Migration and Suppresses the Response of HNSCC Cells to Cisplatin
2.4. The Effects of Collagen Are Mediated through DDR1 in HNSCC Cells
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Tissue Samples
4.2. RNA Sequencing and Bioinformatics
4.3. Analysis of DDR1 Expression in the Cancer Genome Atlas HNSCC Data Set
4.4. Western Blotting
4.5. Immunohistochemistry
4.6. Cell Proliferation Assays
4.7. Transwell Migration and Invasion Assays
4.8. Annexin V-FITC/ Propidium Iodide (PI) Apoptosis Assays
4.9. Reverse Transcription-Quantitative PCR (RT-qPCR)
4.10. Knockdown of DDR1
4.11. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Warnakulasuriya, S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009, 45, 309–316. [Google Scholar] [CrossRef] [PubMed]
- Speight, P.; Farthing, P. The pathology of oral cancer. Br. Dent. J. 2018, 225, 841. [Google Scholar] [CrossRef] [PubMed]
- Mehanna, H.; Beech, T.; Nicholson, T.; El-Hariry, I.; McConkey, C.; Paleri, V.; Roberts, S. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer—Systematic review and meta-analysis of trends by time and region. Head Neck 2013, 35, 747–755. [Google Scholar] [CrossRef] [PubMed]
- Leemans, C.R.; Snijders, P.J.; Brakenhoff, R.H. The molecular landscape of head and neck cancer. Nat. Rev. Cancer 2018, 18, 269–282. [Google Scholar] [CrossRef]
- Prime, S.; Cirillo, N.; Hassona, Y.; Lambert, D.; Paterson, I.; Mellone, M.; Thomas, G.; James, E.; Parkinson, E. Fibroblast activation and senescence in oral cancer. J. Oral Pathol. Med. 2017, 46, 82–88. [Google Scholar] [CrossRef]
- Dourado, M.R.; Guerra, E.N.; Salo, T.; Lambert, D.W.; Coletta, R.D. Prognostic value of the immunohistochemical detection of cancer-associated fibroblasts in oral cancer: A systematic review and meta-analysis. J. Oral Pathol. Med. 2018, 47, 443–453. [Google Scholar] [CrossRef]
- Vogel, W.; Gish, G.D.; Alves, F.; Pawson, T. The discoidin domain receptor tyrosine kinases are activated by collagen. Mol. Cell 1997, 1, 13–23. [Google Scholar] [CrossRef]
- Valiathan, R.R.; Marco, M.; Leitinger, B.; Kleer, C.G.; Fridman, R. Discoidin domain receptor tyrosine kinases: New players in cancer progression. Cancer Metastasis Rev. 2012, 31, 295–321. [Google Scholar] [CrossRef]
- Miao, L.; Zhu, S.; Wang, Y.; Li, Y.; Ding, J.; Dai, J.; Cai, H.; Zhang, D.; Song, Y. Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung cancer and promotes cell invasion via epithelial-to-mesenchymal transition. Med. Oncol. 2013, 30, 626. [Google Scholar] [CrossRef]
- Xie, R.; Wang, X.; Qi, G.; Wu, Z.; Wei, R.; Li, P.; Zhang, D. DDR1 enhances invasion and metastasis of gastric cancer via epithelial-mesenchymal transition. Tumor Biol. 2016, 37, 12049–12059. [Google Scholar] [CrossRef]
- Squire, J.A.; Bayani, J.; Luk, C.; Unwin, L.; Tokunaga, J.; MacMillan, C.; Irish, J.; Brown, D.; Gullane, P.; Kamel-Reid, S. Molecular cytogenetic analysis of head and neck squamous cell carcinoma: By comparative genomic hybridization, spectral karyotyping, and expression array analysis. Head Neck J. Sci. Spec. Head Neck 2002, 24, 874–887. [Google Scholar] [CrossRef] [PubMed]
- Lim, K.P.; Cirillo, N.; Hassona, Y.; Wei, W.; Thurlow, J.K.; Cheong, S.C.; Pitiyage, G.; Parkinson, E.K.; Prime, S.S. Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma. J. Pathol. 2011, 223, 459–469. [Google Scholar] [CrossRef] [PubMed]
- Sok, J.; Lee, J.; Dasari, S.; Joyce, S.; Contrucci, S.; Egloff, A.; Trevelline, B.; Joshi, R.; Kumari, N.; Grandis, J. Collagen type XI α1 facilitates head and neck squamous cell cancer growth and invasion. Br. J. Cancer 2013, 109, 3049. [Google Scholar] [CrossRef] [PubMed]
- Vázquez-Villa, F.; García-Ocaña, M.; Galván, J.A.; García-Martínez, J.; García-Pravia, C.; Menéndez-Rodríguez, P.; González-del Rey, C.; Barneo-Serra, L.; Juan, R. COL11A1/(pro) collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression. Tumor Biol. 2015, 36, 2213–2222. [Google Scholar] [CrossRef]
- Shang, J.; Wang, F.; Chen, P.; Wang, X.; Ding, F.; Liu, S.; Zhao, Q. Co-expression network analysis identified COL8A1 is associated with the progression and prognosis in human colon adenocarcinoma. Dig. Dis. Sci. 2018, 63, 1219–1228. [Google Scholar] [CrossRef]
- Zhao, Y.; Jia, L.; Mao, X.; Xu, H.; Wang, B.; Liu, Y. siRNA-targeted COL8A1 inhibits proliferation, reduces invasion and enhances sensitivity to D-limonence treatment in hepatocarcinoma cells. IUBMB Life 2009, 61, 74–79. [Google Scholar] [CrossRef]
- Mellone, M.; Hanley, C.; Thirdborough, S.; Mellows, T.; Garcia, E.; Woo, J.; Tod, J.; Frampton, S.; Venei, V.; Moutasim, K. Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis. Aging (Albany NY) 2016, 9, 114–131. [Google Scholar] [CrossRef]
- Kumari, K.; Ghosh, S.; Patil, S.; Augustine, D.; Samudrala Venkatesiah, S.; Rao, R.S. Expression of type III collagen correlates with poor prognosis in oral squamous cell carcinoma. J. Investig. Clin. Dent. 2017, 8, e12253. [Google Scholar] [CrossRef]
- Huo, Y.; Yang, M.; Liu, W.; Yang, J.; Fu, X.; Liu, D.; Li, J.; Zhang, J.; Hua, R.; Sun, Y. High expression of DDR1 is associated with the poor prognosis in Chinese patients with pancreatic ductal adenocarcinoma. J. Exp. Clin. Cancer Res. 2015, 34, 88. [Google Scholar] [CrossRef]
- Hur, H.; Ham, I.-H.; Lee, D.; Jin, H.; Aguilera, K.Y.; Oh, H.J.; Han, S.-U.; Kwon, J.E.; Kim, Y.-B.; Ding, K. Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric carcinoma. BMC Cancer 2017, 17, 87. [Google Scholar] [CrossRef]
- Aguilera, K.Y.; Huang, H.; Du, W.; Hagopian, M.M.; Wang, Z.; Hinz, S.; Hwang, T.H.; Wang, H.; Fleming, J.B.; Castrillon, D.H. Inhibition of discoidin domain receptor 1 reduces collagen-mediated tumorigenicity in pancreatic ductal adenocarcinoma. Mol. Cancer Ther. 2017, 16, 2473–2485. [Google Scholar] [CrossRef] [PubMed]
- Cader, F.Z.; Vockerodt, M.; Bose, S.; Nagy, E.; Brundler, M.-A.; Kearns, P.; Murray, P.G. The EBV oncogene LMP1 protects lymphoma cells from cell death through the collagen-mediated activation of DDR1. Blood 2013, 122, 4237–4245. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, X.-H.; Feng, Z.-E.; Yan, M.; Hanada, S.; Zuo, H.; Yang, C.-Z.; Han, Z.-G.; Guo, W.; Chen, W.-T.; Zhang, P. XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer. PLoS ONE 2012, 7, e31601. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Liu, X.Q.; Hou, J.S.; Wang, J.N.; Huang, H.Z. Molecular mechanisms of chemoresistance in oral cancer. Chin. J. Dent. Res. 2016, 19, 25–33. [Google Scholar] [PubMed]
- Vogel, W.F.; Aszódi, A.; Alves, F.; Pawson, T. Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Mol. Cell. Biol. 2001, 21, 2906–2917. [Google Scholar] [CrossRef] [PubMed]
- Schminke, B.; Muhammad, H.; Bode, C.; Sadowski, B.; Gerter, R.; Gersdorff, N.; Bürgers, R.; Monsonego-Ornan, E.; Rosen, V.; Miosge, N. A discoidin domain receptor 1 knock-out mouse as a novel model for osteoarthritis of the temporomandibular joint. Cell. Mol. Life Sci. 2014, 71, 1081–1096. [Google Scholar] [CrossRef] [PubMed]
- Leitinger, B. Discoidin domain receptor functions in physiological and pathological conditions. In International Review of Cell and Molecular Biology; Elsevier: Amsterdam, The Netherlands, 2014; Volume 310, pp. 39–87. [Google Scholar]
- Hassona, Y.; Cirillo, N.; Lim, K.P.; Herman, A.; Mellone, M.; Thomas, G.J.; Pitiyage, G.N.; Parkinson, E.K.; Prime, S.S. Progression of genotype-specific oral cancer leads to senescence of cancer-associated fibroblasts and is mediated by oxidative stress and TGF-beta. Carcinogenesis 2013, 34, 1286–1295. [Google Scholar] [CrossRef]
- White, J.S.; Weissfeld, J.L.; Ragin, C.C.; Rossie, K.M.; Martin, C.L.; Shuster, M.; Ishwad, C.S.; Law, J.C.; Myers, E.N.; Johnson, J.T. The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol. 2007, 43, 701–712. [Google Scholar] [CrossRef] [Green Version]
- Steenbergen, R.D.; Hermsen, M.A.; Walboomers, J.M.; Joenje, H.; Arwert, F.; Meijer, C.J.; Snijders, P.J. Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and 18q21 in an oral carcinoma and its derivative cell line. Cancer Res. 1995, 55, 5465–5471. [Google Scholar]
- Hay, A.; Ganly, I. Targeted therapy in oropharyngeal squamous cell carcinoma: The implications of HPV for therapy. Rare Cancers Ther. 2015, 3, 89–117. [Google Scholar] [CrossRef]
- Law, C.W.; Chen, Y.; Shi, W.; Smyth, G.K. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014, 15, R29. [Google Scholar] [CrossRef] [PubMed]
- Mootha, V.K.; Lindgren, C.M.; Eriksson, K.-F.; Subramanian, A.; Sihag, S.; Lehar, J.; Puigserver, P.; Carlsson, E.; Ridderstråle, M.; Laurila, E. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 2003, 34, 267–273. [Google Scholar] [CrossRef] [PubMed]
- Subramanian, A.; Tamayo, P.; Mootha, V.K.; Mukherjee, S.; Ebert, B.L.; Gillette, M.A.; Paulovich, A.; Pomeroy, S.L.; Golub, T.R.; Lander, E.S. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 2005, 102, 15545–15550. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liberzon, A.; Subramanian, A.; Pinchback, R.; Thorvaldsdóttir, H.; Tamayo, P.; Mesirov, J.P. Molecular signatures database (MSigDB) 3.0. Bioinformatics 2011, 27, 1739–1740. [Google Scholar] [CrossRef] [PubMed]
- Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015, 517, 576–582. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Robinson, M.D.; McCarthy, D.J.; Smyth, G.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26, 139–140. [Google Scholar] [CrossRef]
- R Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2018. [Google Scholar]
- Ambrogio, C.; Gómez-López, G.; Falcone, M.; Vidal, A.; Nadal, E.; Crosetto, N.; Blasco, R.B.; Fernández-Marcos, P.J.; Sánchez-Céspedes, M.; Ren, X. Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma. Nat. Med. 2016, 22, 270–277. [Google Scholar] [CrossRef]
- Wang, Z.; Zhang, Y.; Bartual, S.G.; Luo, J.; Xu, T.; Du, W.; Xun, Q.; Tu, Z.; Brekken, R.A.; Ren, X. Tetrahydroisoquinoline-7-carboxamide derivatives as new selective discoidin domain receptor 1 (DDR1) inhibitors. ACS Med. Chem. Lett. 2017, 8, 327–332. [Google Scholar] [CrossRef]
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Lai, S.L.; Tan, M.L.; Hollows, R.J.; Robinson, M.; Ibrahim, M.; Margielewska, S.; Parkinson, E.K.; Ramanathan, A.; Zain, R.B.; Mehanna, H.; et al. Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1. Cancers 2019, 11, 1766. https://doi.org/10.3390/cancers11111766
Lai SL, Tan ML, Hollows RJ, Robinson M, Ibrahim M, Margielewska S, Parkinson EK, Ramanathan A, Zain RB, Mehanna H, et al. Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1. Cancers. 2019; 11(11):1766. https://doi.org/10.3390/cancers11111766
Chicago/Turabian StyleLai, Sook Ling, May Leng Tan, Robert J. Hollows, Max Robinson, Maha Ibrahim, Sandra Margielewska, E. Kenneth Parkinson, Anand Ramanathan, Rosnah Binti Zain, Hisham Mehanna, and et al. 2019. "Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1" Cancers 11, no. 11: 1766. https://doi.org/10.3390/cancers11111766