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Profiling Signal Pathway Activation during Lymphangiogenesis
Author(s) -
Leak Lee Virn,
Petrocion Emanuel F.,
Liotta Lance A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1216-c
Subject(s) - lymphangiogenesis , lymphatic endothelium , angiogenesis , protein kinase b , microbiology and biotechnology , lymphatic system , mapk/erk pathway , signal transduction , proteome , cancer research , biology , chemistry , immunology , medicine , bioinformatics , metastasis , cancer
A number of studies have shown that VEGF‐C is a potent mitogen for the lymphatic endothelium and a key lymphangiogenic factor. However, the biochemical signaling pathways activated via VEGFR‐3 upon stimulation by VEGF‐C in the lymphatic endothelium (LEC) are not well defined. We have employed an in vitro cell culture model of lymphangiogenesis to profile protein phosphorylation coupled with reverse‐phase protein microarrays and phosphor‐specific antibodies. The goal is to examine the activation status of key molecular steps in LEC survival, proliferation signaling leading to differentiation. With VEGF‐C stimulation, the levels of activated ERK showed correlations between proliferating status versus tube forming. In addition, p38 showed variations in LEC stimulated with VEGF‐C and marked changes were noted between the various stages of lymphangiogenesis for phospho‐p38 and total p38, of the MAPKK pathway. Activated AKT, an indicator of the state of PI3kinase/AKT pro‐survival pathway exhibited intense activation within the different stages of lymphangiogenesis. These results support a different mechanism for lymphangiogenesis versus blood endothelial angiogenesis, and is in keeping with our previous results showing that the lymph proteome is distinct from the plasma proteome. By employing this high throughput technology for the analysis of signal pathway profiling in LEC during lymphangiogenesis it will be possible to gain further insight into the molecular modification of proteins in the lymphatic endothelium during various physiological and pathological conditions.