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.
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.
Chen
Maria J
MJ
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269, USA.
Chiou
Pinwen Peter
PP
Lin
Patrick
P
Lin
Chun-Mean
CM
Siri
S
S
Peck
Konan
K
Chen
Thomas T
TT
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D017686:Oncorhynchus mykiss; D010455:Peptides / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology
D010455:Peptides; D011498:Protein Precursors; D011994:Recombinant Proteins; C119953:pro-insulin-like growth factor I; D007334:Insulin-Like Growth Factor I