A host deficiency of discoidin domain receptor 2 (DDR2) inhibits both tumour angiogenesis and metastasis
| Autor: | Shuya, Zhang, Xin, Bu, Hu, Zhao, Jiangtian, Yu, Yingmei, Wang, Di, Li, Chuchao, Zhu, Tong, Zhu, Tingting, Ren, Xinping, Liu, Libo, Yao, Jin, Su |
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| Rok vydání: | 2013 |
| Předmět: |
Mice
Knockout Lung Neoplasms Skin Neoplasms Time Factors Genotype Neovascularization Pathologic Melanoma Experimental Endothelial Cells Neovascularization Physiologic Receptor Protein-Tyrosine Kinases Transfection Tumor Burden Mice Phenotype Cell Movement Cell Line Tumor Receptors Mitogen Human Umbilical Vein Endothelial Cells Tumor Microenvironment Animals Humans Neoplasm Invasiveness Discoidin Domain Receptors Cell Proliferation |
| Zdroj: | The Journal of pathology. 232(4) |
| ISSN: | 1096-9896 |
| Popis: | Discoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK) that signals in response to collagen binding and is implicated in tumour malignant phenotypes such as invasion and metastasis. Although it has been reported that DDR2 expression is up-regulated in activated endothelial cells (ECs), functional studies are lacking. Herein, we found that enforced expression of DDR2 promoted proliferation, migration and tube formation of primary human umbilical vein endothelial cells (HUVECs). The results of immunohistochemical analysis showed a strikingly high level of DDR2 in human tumour ECs. Most significantly, we discovered that a host deficiency of DDR2 inhibits subcutaneous angiogenesis induced by either VEGF or tumour cells. In addition, the remaining tumour vessels in DDR2-deficient mice exhibit some normalized properties. These vascular phenotypes are accompanied by the up-regulation of anti-angiogenic genes and down-regulation of pro-angiogenic genes, as well as by alleviated tumour hypoxia. By use of a tail vein metastasis model of melanoma, we uncovered that loss of stromal DDR2 also suppresses tumour metastasis to the lung. Hence, our current data disclose a new mechanism by which DDR2 affects tumour progression, and may strengthen the feasibility of targeting DDR2 as an anticancer strategy. |
| Databáze: | OpenAIRE |
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