Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model
- Equal contributors
1 Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
2 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
3 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, School of Medicine, Baltimore, MD 21231, USA
4 Monash Institute of Medical Research, Monash Medical Centre, Victoria, Australia
5 Roswell Park Cancer Institute, Buffalo, New York 14263, USA
BMC Cancer 2010, 10:29 doi:10.1186/1471-2407-10-29Published: 1 February 2010
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.
One family of peptides with high activity is derived from the α-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 α5 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.
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.
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.