NDLI: Differential TIMP3 expression affects tumor progression and angiogenesis in melanomas through regulation of directionally persistent endothelial cell migration

Content Provider	Springer Nature Link
Author	Das, Asha M. Seynhaeve, Ann L. B. Rens, Joost A. P. Vermeulen, Cindy E. Koning, Gerben A. Eggermont, Alexander M. M. ten Hagen, Timo L. M.
Copyright Year	2013
Abstract	The angiogenic potential of solid tumors, or the ability to initiate neovasculature development from pre-existing host vessels, is facilitated by soluble factors secreted by tumor cells and involves breaching of extracellular matrix barriers, endothelial cell (EC) proliferation, migration and reassembly. We evaluated the angiogenic potential of human melanoma cell lines differing in their degree of aggressiveness, based on their ability to regulate directionally persistent EC migration. We observed that conditioned-medium (CM) of the aggressive melanoma cell line BLM induced a high effective migratory response in ECs, while CMs of Mel57 and 1F6 had an inhibitory effect. Further, the melanoma cell lines exhibited a varied expression profile of tissue inhibitor of metalloproteinase-3 (TIMP3), detectable in the CM. TIMP3 expression inversely correlated with aggressiveness of the melanoma cell line, and ability of the respective CMs to induce directed EC migration. Interestingly, TIMP3 expression was found to be silenced in the BLM cell line, concurrent with its role as a tumor suppressor. Treatment with recombinant human TIMP3 and CM of modified, TIMP3 expressing, BLM cells mitigated directional EC migration, while CM of TIMP3 silenced 1F6 cells induced directed EC migration. The functional implication of TIMP3 expression on tumor growth and angiogenic potential in melanoma was evaluated in vivo. We observed that TIMP3 expression reduced tumor growth, angiogenesis and macrophage infiltration of BLM tumors while silencing TIMP3 increased tumor growth and angiogenesis of 1F6 tumors. Taken together, our results demonstrate that TIMP3 expression correlates with inhibition of directionally persistent EC migration and adversely affects the angiogenic potential and growth of melanomas.
Starting Page	163
Ending Page	177
Page Count	15
File Format	PDF
ISSN	09696970
Journal	Angiogenesis
Volume Number	17
Issue Number	1
e-ISSN	15737209
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-09-25
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	TIMP3 Melanoma Angiogenic potential Directional endothelial cell migration Cancer Research Biomedicine general Cell Biology Cardiology Ophthalmology Oncology
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Cancer Research

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