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The p38 MAPK signaling pathway contributes to tumor‐induced angiogenesis
Author(s) -
Rajashekhar Gangaraju,
Suckow Mark,
Kamocka Malgorzata,
Rosen Elliot,
Clauss Matthias
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.a747-c
Subject(s) - angiogenesis , mapk/erk pathway , proinflammatory cytokine , cancer research , signal transduction , p38 mitogen activated protein kinases , inflammation , medicine , microbiology and biotechnology , biology , immunology
There is increasing evidence that chronic inflammation is tightly linked to diseases associated with endothelial dysfunction including aberrant angiogenesis. We propose that this proinflammatory setting in tumors can alter the angiogenic mechanism and provide a basis for selectively treating tumors with antiangiogenic strategies. To address the hypothesis that these proinflammatory and proangiogenic conditions in tumors, elicit signaling pathways, which are distinct from the angiogenic pathways of physiological angiogenesis, we compared signaling pathways in control and continuously activated endothelial cells. In fact, we could demonstrate a signaling switch from Erk‐1/2 to p38 MAPK pathways in angiogenesis in vitro when shifting from control to activated conditions. When testing this hypothesis in vivo using experimental prostate tumors, pharmacological inhibition of p38 MAPK demonstrated a significant reduction in angiogenesis and tumor growth. These results support our conclusions from in vitro that under pathological conditions the stress associated p38 MAPK prevails. Together, our results suggest that the identification of this tumor angiogenesis‐selective pathway may lead to improved antiangiogenic tumor therapy with reduced side effects on physiological angiogenesis such as in wound repair. This work is supported by the Indiana Center for Vascular Biology & Medicine.