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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric carcinoma

Authors: Hoon Hur, In-Hye Ham, Dakeun Lee, Hyejin Jin, Kristina Y. Aguilera, Hye Jeong Oh, Sang-Uk Han, Ji Eun Kwon, Young-Bae Kim, Ke Ding, Rolf A. Brekken

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that utilizes collagen as a ligand, is a key molecule in the progression of solid tumors as it regulates the interaction of cancer cells with the tumor stroma. However, the clinical relevance of DDR1 expression in gastric carcinoma is yet to be investigated. Here, we assessed the role of DDR1 in mediating the aggressive phenotype of gastric carcinoma and its potential as a therapeutic target.

Methods

We conducted DDR1 immunohistochemistry using a tissue microarray of 202 gastric carcinoma specimens. We examined the effect of collagen-induced activation of DDR1 on cell signaling, tumorigenesis, and cell migration in gastric cancer cell lines, and tumor growth in a xenograft animal model of gastric cancer.

Results

Our results showed that 50.5% of gastric cancer tissues are positive for DDR1 expression, and positive DDR1 expression was significantly correlated with a poor prognosis (P = 0.015). In a subgroup analysis, DDR1 expression was prognostically meaningful only in patients receiving adjuvant treatment (P = 0.013). We also demonstrated that collagen was able to activate DDR1 and increase the clonogenicity and migration of gastric cancer cells. We observed that a DDR1 inhibitor, 7rh benzamide, suppressed tumor growth in gastric cancer xenografts.

Conclusions

Our findings suggest a key role for DDR1 signaling in mediating the aggressive phenotype of gastric carcinoma. Importantly, inhibition of DDR1 is an attractive strategy for gastric carcinoma therapy.
Appendix
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Metadata
Title
Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric carcinoma
Authors
Hoon Hur
In-Hye Ham
Dakeun Lee
Hyejin Jin
Kristina Y. Aguilera
Hye Jeong Oh
Sang-Uk Han
Ji Eun Kwon
Young-Bae Kim
Ke Ding
Rolf A. Brekken
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3051-9

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