0000000000729602
AUTHOR
Scott William Rowlinson
Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant
Abstract Despite intense research and clinical efforts, patients affected by advanced colorectal cancer (CRC) have still a poor prognosis. The discovery of colorectal (CR) cancer stem cell (CSC) as the cell compartment responsible for tumor initiation and propagation may provide new opportunities for the development of new therapeutic strategies. Given the reduced sensitivity of CR-CSCs to chemotherapy and the ability of bone morphogenetic proteins (BMP) to promote colonic stem cell differentiation, we aimed to investigate whether an enhanced variant of BMP7 (BMP7v) could sensitize to chemotherapy-resistant CRC cells and tumors. Thirty-five primary human cultures enriched in CR-CSCs, includ…
A BMP7 Variant Inhibits Tumor Angiogenesis In Vitro and In Vivo through Direct Modulation of Endothelial Cell Biology
Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v) in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating …
Abstract B5: A BMP7 variant inhibits angiogenesis in vitro and in vivo in part by downregulating VEGFR2 and FGFR1 expression in endothelial cells.
Abstract Glioblastoma multiforme (GBM), the most aggressive glioma, requires active angiogenesis for growth and survival. Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Previously, we demonstrated the use of a BMP7 variant (BMP7v) to differentiate glioblastoma stem-like cells (GSLCs) and significantly reduce their tumorigenic potential (Tate and Pallini et al. 2012). Using an in vitro co-culture endothelial cord formation assay, a surrogate of angiogenesis, and its cognate in vivo model, we investigated the role of BMP7v in VEGF, basic FGF (bFGF), tumor-driven a…