Abstract
BackgroundAngiogenesis 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.MethodsOne 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.ResultsPentastatin-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.ConclusionsThe 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.
Highlights
Angiogenesis is the formation of neovasculature from a pre-existing vascular network
Judah Folkman pioneered the field of tumor angiogenesis by demonstrating that solid tumors are dependent on their blood supply to grow and metastasize, placing the field of tumor angiogenesis at the center of cancer biology and therapeutics [1]
We recently developed a bioinformatics-based approach to predict over 100 novel endogenous antiangiogenic peptides [10]
Summary
Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. The over-expression of vascular endothelial growth factor (VEGF) has been correlated with rapid small cell lung cancer (SCLC) growth [8]. SCLC makes up only 20% of lung cancer cases, its characteristics have been described as extremely virulent - correlated with rapid cell growth, high resistance to chemotherapy, and low median survival [9]. These factors correlate with a shorter relapse-free and overall survival, indicating the necessity for comprehensive treatment
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