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Unfolded protein response inhibits capillary endothelial cell invasion in Matrigel TM
Author(s) -
Montiel Maria F,
Saha Subiman,
Trujillo Uldaleiz,
Milan Maria T,
Banerjee Dipak K
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.a1010
Subject(s) - tunicamycin , matrigel , angiogenesis , endothelial stem cell , microbiology and biotechnology , chemistry , biology , cancer research , apoptosis , unfolded protein response , biochemistry , in vitro
Angiogenesis is the formation of new capillaries from pre‐existing vasculature, and is a ‘key’ to tumor growth and invasion. A large number of cytokines accelerate the process of angiogenesis by helping to control a switch in the angiogenic phenotype which enhances glycosylation of asparagine‐linked (N‐linked) glycoproteins. Our objective has been to understand the molecular basis of the angiogenic process so that appropriate glyco‐therapeutics could be developed against the breast cancer. Using an antibiotic and a protein N‐glycosylation inhibitor tunicamycin our laboratory has recently observed that a non‐transformed capillary endothelial cell line when treated with tunicamycin the cell cycle was arrested in G1 and developed apoptosis by inducing unfolded protein response (upr). In addition, there was reduced expression of matrix metalloproteinase‐1 (MMP1) in tunicamycin‐treated cells. To test the hypothesis that tunicamycin inhibits endothelial cell invasion, a synchronized culture of capillary endothelial cells was seeded on growth factor reduced Matrigel( coated plates and examined after 24 hours. We have used the conditioned media from MCF‐7 human breast cancer cells as a chemoattractant. The results indicated that tunicamycin (1 μg/ml) inhibited the cell migration through the Matrigel. Supported by NIH U54‐CA096297 and the Susan G. Komen Breast Cancer Foundation BCTR58206 grants.