Premium
Notch signaling mediates melanoma–endothelial cell communication and melanoma cell migration
Author(s) -
Howard Jason D.,
Moriarty Whei F.,
Park JinSeok,
Riedy Katherine,
Panova Izabela P.,
Chung Christine H.,
Suh KahpYang,
Levchenko Andre,
Alani Rhoda M.
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12131
Subject(s) - melanoma , cancer research , stromal cell , endothelial stem cell , notch signaling pathway , tumor microenvironment , biology , cell , signal transduction , cell signaling , cell growth , microbiology and biotechnology , tumor cells , genetics , in vitro
Summary Stromal and cellular components within the tumor microenvironment significantly influence molecular signals mediating tumor growth and progression. We recently performed a screen to evaluate critical mediators of melanoma–endothelial communication and identified several molecular pathways associated with these cellular networks, including Notch3. Here, we evaluate the nature of melanoma–endothelial communication mediated by Notch3 and its functional significance. We find that Notch3 is specifically upregulated in melanoma–endothelial cell cocultures and is functionally associated with increased Notch signaling in melanoma cells. Furthermore, induced Notch3 signaling in melanoma cell lines leads to enhanced tumor cell migration without associated increases in tumor cell growth. Additionally, Notch3 expression is specifically associated with malignant patient samples and is not evident in benign nevi. We conclude that Notch3 mediates melanoma–endothelial cell communication and tumor cell migration and may serve as a meaningful therapeutic target for this aggressive malignancy.