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Suppression of growth and cancer‐induced angiogenesis of aggressive human breast cancer cells (MDA‐MB‐231) on the chorioallantoic membrane of developing chicken embryos by E‐peptide of pro‐IGF‐I
Author(s) -
Chen Maria J.,
Peter Chiou Pinwen,
Lin Patrick,
Lin ChunMean,
Siri S.,
Peck Konan,
Chen Thomas T.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21254
Subject(s) - angiogenesis , chorioallantoic membrane , biology , cancer cell , growth factor , microbiology and biotechnology , peptide , cell growth , embryo , cancer research , cancer , biochemistry , receptor , genetics
Abstract E‐peptide of the pro‐Insulin‐like growth factor‐I (pro‐IGF‐I) is produced from pre‐pro‐IGF‐I by proteolytic cleavage in the post‐translational processing. Previous in vitro studies conducted in our laboratory showed that Ea4‐peptide of rainbow trout (rt) pro‐IGF‐I or Eb‐peptide of human (h) pro‐IGF‐I exhibited activities including induction of morphological differentiation, inhibition of anchorage‐independent cell growth and suppression of invasion of several well established human cancer cell lines such as MDA‐MB‐231, HT‐29, SK‐N‐F1, and HepG‐2 (Chen et al. [2002] Gen Comp Endocrinol 126:342–351; Kuo and Chen [2002] Exp Cell Res 280:75–89). Seeding of aggressive human breast cancer cells, MDA‐MB‐231, on the chorioallantoic membrane (CAM) of 5 days old chicken embryos resulted in rapid growth and invasion of the cells and induction of blood vessel formation around the MDA‐MB‐231 cell mass in the chicken embryos. The invasion of MDA‐MB‐231 cells in the chicken embryos was further confirmed by immunocytochemistry. The rapid growth and invasion of MDA‐MB‐231 cells and the induction of blood vessel formation by MDA‐MB‐231 cells on chicken CAM are inhibited by treatment with a single or multiple doses of rtEa4‐ or hEb‐peptide. Furthermore, a dose‐dependent inhibition of angiogenesis by rtEa4‐ or hEb‐peptide was also demonstrated by the chicken CAM assay. Results of microarray analysis of human gene chips (containing 9,500 unique cDNA clones) and confirmation by comparative real‐time RT‐PCR analysis showed that a group of genes related to cancer cell activities are up‐ or down‐regulated in MDA‐MB‐231 cells transfected with a rtEa4‐peptide gene. Together these results confirm the anti‐tumor activity of rtEa4‐ and hEb‐peptides, and further suggest that these peptides could be developed as therapeutics for treating human cancers. J. Cell. Biochem. 101:1316–1327, 2007. © 2007 Wiley‐Liss, Inc.