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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lo PH,Lung HL,Cheung AK,Apte SS,Chan KW,Kwong FM,Ko JM,Cheng Y,Law S,Srivastava G,Zabarovsky ER,Tsao SW,Tang JC,Stanbridge EJ,Lung MLdoi
10.1158/0008-5472.CAN-09-4510subject
Has Abstractpub_date
2010-07-01 00:00:00pages
5567-76issue
13eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-09-4510journal_volume
70pub_type
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