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- W2914503715 abstract "Angiogenesis is critical for breast cancer progression. Overexpression of HER-2/neu receptors occur in 25–30% of breast cancers, and treatment with trastuzumab inhibits HER-2-overexpressing tumor growth. Notably, HER-2-mediated signaling enhances vascular endothelial growth factor (VEGF) secretion to increase tumor-associated angiogenesis. Squalamine (aminosterol compound) suppresses VEGF-induced activation of kinases in vascular endothelial cells and inhibits tumor-associated angiogenesis. We assessed antitumor effects of squalamine either alone or with trastuzumab in nude mice bearing breast tumor xenografts without (MCF-7) or with HER2-overexpression (MCF-7/HER-2). Squalamine alone inhibited progression of MCF-7 tumors lacking HER2 overexpression, and squalamine combined with trastuzumab elicited marked inhibition of MCF-7/HER2 growth exceeding that of trastuzumab alone. MCF-7/HER-2 cells secrete higher levels of VEGF than MCF-7 cells, but squalamine elicited no growth inhibition of either MCF-7/HER-2 or MCF-7 cells in vitro. However, squalamine did stop growth of human umbilical vein endothelial cells (HUVECs) and reduced VEGF-induced endothelial tube-like formations in vitro. These effects correlated with blockade of focal adhesion kinase phosphorylation and stress fiber assembly in HUVECs. Thus, squalamine effectively inhibits growth of breast cancers with or without HER-2-overexpression, an effect due in part to blockade of tumor-associated angiogenesis." @default.
- W2914503715 created "2019-02-21" @default.
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- W2914503715 creator A5037339339 @default.
- W2914503715 creator A5047556602 @default.
- W2914503715 creator A5068958299 @default.
- W2914503715 date "2019-05-01" @default.
- W2914503715 modified "2023-10-18" @default.
- W2914503715 title "Squalamine blocks tumor-associated angiogenesis and growth of human breast cancer cells with or without HER-2/neu overexpression" @default.
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- W2914503715 doi "https://doi.org/10.1016/j.canlet.2019.02.009" @default.
- W2914503715 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6598711" @default.
- W2914503715 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30771431" @default.
- W2914503715 hasPublicationYear "2019" @default.
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