Self-Assembly of Sulfate-Containing Peptides Sequesters VEGF for Inhibiting Cancer Cell Invasion

Abstract

Heparan sulfate proteoglycans (HSPGs) play a crucial role in regulating cancer growth and migration by mediating interactions with growth factors. In this study, we developed a self-assembling peptide (S1) containing a sulfate group to simulate the contiguous sulfated regions (S-domains) in heparan sulfate for growth factor binding, aiming to sequester growth factors like VEGF. Spectral and structural studies as well as simulation studies suggested that S1 self-assembled into nanostructures similar to the heparan sulfate chains and effectively bound to VEGF. On cancer cell surfaces, S1 self-assemblies sequestered VEGF, leading to a reduction in VEGF levels in the medium, consequently inhibiting cancer cell growth, invasion, and angiogenesis. This study highlights the potential of self-assembling peptides to emulate extracellular matrix functions, offering insights for future cancer therapeutic strategies.

Applications of self-assembled peptide hydrogels in anti-tumor therapy

“…This sequence self-assembled into nanobers on the surfaces of tumor cells to sequester vascular endothelial growth factor (VEGF), thereby inhibiting the growth, invasion and angiogenesis of cancer cells. 32 RGD, a short peptide made up of the amino acids arginine (R), glycine (G), and aspartic acid (D), is widely present in the extracellular matrix proteins. It can prevent tumor cells from adhering to the extracellular matrix by competitively binding to integrin receptors or directly inducing tumor cell death, resulting in the suppression of tumor cell proliferation, invasion, and metastasis.…”

“…This sequence self-assembled into nanofibers on the surfaces of tumor cells to sequester vascular endothelial growth factor (VEGF), thereby inhibiting the growth, invasion and angiogenesis of cancer cells. 32 …”