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  • Beta2 glycoprotein I-derived therapeutic peptides induce sFlt-1 secretion to reduce melanoma vascularity and growth.

Beta2 glycoprotein I-derived therapeutic peptides induce sFlt-1 secretion to reduce melanoma vascularity and growth.

Cancer letters (2020-09-07)
Haley Smalley, Jennifer M Rowe, Fernando Nieto, Jazmin Zeledon, Kellyn Pollard, John M Tomich, Sherry D Fleming
ABSTRACT

Melanoma, a form of skin cancer, is one of the most common cancers in young men and women. Tumors require angiogenesis to provide oxygen and nutrients for growth. Pro-angiogenic molecules such as VEGF and anti-angiogenic molecules such as sFlt-1 control angiogenesis. In addition, the serum protein, Beta2 Glycoprotein I (β2-GPI) induces or inhibits angiogenesis depending on conformation and concentration. β2-GPI binds to proteins and negatively charged phospholipids on hypoxic endothelial cells present in the tumor microenvironment. We hypothesized that peptides derived from the binding domain of β2-GPI would regulate angiogenesis and melanoma growth. In vitro analyses determined the peptides reduced endothelial cell migration and sFlt-1 secretion. In a syngeneic, immunocompetent mouse melanoma model, β2-GPI-derived peptides also reduced melanoma growth in a dose-dependent response with increased sFlt-1 and attenuated vascular markers compared to negative controls. Importantly, administration of peptide with sFlt-1 antibody resulted in tumor growth. These data demonstrate the therapeutic potential of novel β2-GPI-derived peptides to attenuate tumor growth and endothelial migration is sFlt-1 dependent.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Human VEGFR1 ELISA Kit, for cell culture supernatants, plasma, and serum samples