Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/32761
Title: Extracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis
Authors: Lo, PHY
Lung, HL
Cheung, AKL
Apte, SS
Chan, KW
Kwong, FM
Ko, JMY
Cheng, Y
Law, S
Srivastava, G
Zabarovsky, ER
Tsao, SW
Tang, JCO 
Stanbridge, EJ
Lung, ML
Issue Date: 2010
Publisher: Amer Assoc Cancer Research
Source: Cancer research, 2010, v. 70, no. 13, p. 5567-5576 How to cite?
Journal: Cancer Research 
Abstract: ADAMTS metalloprotease family member ADAMTS9 maps to 3p14.2 and shows significant associations with the aerodigestive tract cancers esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). However, the functional impact of ADAMTS9 on cancer development has not been explored. In this study, we evaluated the hypothesized antiangiogenic and tumor-suppressive functions of ADAMTS9 in ESCC and NPC, in stringent tumorigenicity and Matrigel plug angiogenesis assays. ADAMTS9 activation suppressed tumor formation in nude mice. Conversely, knockdown of ADAMTS9 resulted in clones reverting to the tumorigenic phenotype of parental cells. In vivo angiogenesis assays revealed a reduction in microvessel numbers in gel plugs injected with tumor-suppressive cell transfectants. Similarly, conditioned medium from cell transfectants dramatically reduced the tube-forming capacity of human umbilical vein endothelial cells. These activities were associated with a reduction in expression levels of the proangiogenic factors MMP9 and VEGFA, which were consistently reduced in ADAMTS9 transfectants derived from both cancers. Taken together, our results indicate that ADAMTS9 contributes an important function in the tumor microenvironment that acts to inhibit angiogenesis and tumor growth in both ESCC and NPC.
URI: http://hdl.handle.net/10397/32761
DOI: 10.1158/0008-5472.CAN-09-4510
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