Abstract
We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.
Highlights
Angiogenesis is a critical factor in tumor development, and anticancer therapies targeting angiogenesis are being extensively investigated [1,2,3]
We have shown that earlier analogs of SP2024 have antiangiogenic and anti-lymphangiogenic activities in vitro and in vivo [10,14,15]
We examined these effects in three different cell lines: Human umbilical vein endothelial cells (HUVEC) for anti-angiogenic activity, lymphatic endothelial cells (LEC) for anti-lymphangiogenic activity, and MDA-MB-231 tumor cells for anti-tumorigenic activity
Summary
Angiogenesis is a critical factor in tumor development, and anticancer therapies targeting angiogenesis are being extensively investigated [1,2,3]. These investigations have led to the clinical use of anti-angiogenic agents, such as the anti-vascular endothelial growth factor (VEGF) antibody Bevacizumab for breast and other cancers [4,5,6], and small molecule tyrosine kinase inhibitors such as Sunitinib [7]. Their small size leads to good tumor penetration, they have high binding specificity, are flexible to modifications with different tags, and they can be conjugated with other drugs. Integrins serve as co-receptors for many different receptor tyrosine kinases that regulate angiogenesis such as VEGFR, FGFR, HGFR, IGFR [17,18]
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