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Potentiation of angiogenic switch in capillary endothelial cells by cAMP: A cross‐talk between up‐regulated lipid‐linked oligosaccharide biosynthesis and the HSP‐70 expression
Author(s) -
Banerjee Dipak K.,
Martinez Juan A.
Publication year - 2006
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.20.4.a57-d
Subject(s) - microbiology and biotechnology , cell growth , endothelial stem cell , cell culture , biology , intracellular , cell , chemistry , biochemistry , in vitro , genetics
During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium start proliferating. The exact mechanism of switching to a new angiogenic phenotype is currently unknown. We have hypothesized that intracellular cAMP plays a role. When a synchronized non‐transformed capillary endothelial cell line was treated with 2 mM 8Br‐cAMP (i) the cell proliferation was enhanced by ~70%; (ii) the cellular morphology indicated enhanced mitosis; and (iii) almost one‐half of the cell population entered in the S phase in 32 to 40 hours. Bcl‐2 expression and the caspase‐3, ‐8, and ‐9 activity however remained unaffected. On the other hand, there was a significant increase in the lipid‐linked oligosaccharide (LLO; Glc 3 Man 9 GlcNAc 2 ‐PP‐Dol) biosynthesis and turnover, Factor VIIIC N‐glycosylation, and cell surface expression of N‐glycans in 8Br‐cAMP treated cells. Dol‐P‐Man synthase activity in the ER was also increased. Under similar condition there was a significant increase in the cytosolic chaperones HSP‐70 & HSP‐90 expression with a considerable reduction in the ER chaperones GRP‐78/Bip & GRP‐94 expression. We, therefore, conclude that the presence of a high level LLO up‐regulated the expression of HSP‐70 & HSP‐90 expression and down‐regulated that of the GRP‐78/Bip & GRP‐90 in cells treated with 8Br‐cAMP. This reduced ER stress by adequately maintaining the protein folding and prevented apoptosis. As a result capillary endothelial cell proliferation was enhanced. Supported in part by grants DAMD17‐03‐1‐0754 and U54‐CA096297.