Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model.
BACKGROUND
Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays.


METHODS
One family of peptides with high activity is derived from the alpha-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the alpha5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line.


RESULTS
Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model.


CONCLUSIONS
The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.
Koskimaki
Jacob E
JE
Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Karagiannis
Emmanouil D
ED
Tang
Benjamin C
BC
Hammers
Hans
H
Watkins
D Neil
DN
Pili
Roberto
R
Popel
Aleksander S
AS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D024141:Collagen Type IV / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D014471:Umbilical Veins / Q000473:pathology
D000970:Antineoplastic Agents; D024141:Collagen Type IV; D010446:Peptide Fragments; D010455:Peptides; C554448:pentastatin-1 peptide, human