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.

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.

• Authors: Maria J Chen, Pinwen Peter Chiou, Patrick Lin, Chun-Mean Lin, S Siri, Konan Peck, Thomas T Chen
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 101 Issue 5 Pg. 1316-27 (Aug 01 2007) ISSN: 0730-2312 [Print] United States
• PMID: 17286280 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Peptides
• Protein Precursors
• Recombinant Proteins
• pro-insulin-like growth factor I
• Insulin-Like Growth Factor I

Topics

• Animals
• Breast Neoplasms (blood supply, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chick Embryo
• Chorioallantoic Membrane (blood supply)
• Dose-Response Relationship, Drug
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Insulin-Like Growth Factor I (pharmacology, therapeutic use)
• Neoplasm Invasiveness
• Neovascularization, Pathologic (drug therapy)
• Oncorhynchus mykiss
• Peptides (pharmacology)
• Protein Precursors (pharmacology, therapeutic use)
• Recombinant Proteins (pharmacology)