期刊
PROSTAGLANDINS & OTHER LIPID MEDIATORS
卷 89, 期 3-4, 页码 140-146出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2009.07.006
关键词
LPA antagonist; ATX; Engineered tumor xenograft; Lung cancer; Synthetic extracellular matrix; Angiogenesis assay; Phosphonate analog
资金
- NINDS NIH HHS [R01 NS029632, R01 NS029632-17] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS029632] Funding Source: NIH RePORTER
Using an in situ cross-linkable hydrogel that mimics the extracellular matrix (ECM), cancer cells were encapsulated and injected in vivo following a tumor engineering strategy for orthotopic xenografts. Specifically, we created several three-dimensional (3D)human tumor xenografts and evaluated the tumor response to BrP-LPA, a novel dual function LPA antagonist/ATX inhibitor (LPAa/ATXi). First, we describe the model system and the optimization of semi-synthetic ECM (sECM) compositions and injection parameters for engineered xenografts. Second, we summarize a study to compare angiogenesis inhibition in vivo, comparing BrP-LPA to the kinase inhibitor sunitinib maleate (Sutent). Third, we compare treatment of engineered breast tumors with LPAa/ATXi alone with treatment with Taxol. Fourth, using a re-optimized sECM for non-small cell lung cancer cells, we created reproducibly sized subcutaneous lung tumors and evaluated their response to treatment with LPAa/ATXi. Fifth, we summarize the data on the use of LPAa/ATXi to treat a model for colon cancer metastasis to the liver. Taken together, these improved, more realistic xenografts show considerable utility for evaluating the potential of novel anti-metastatic, anti-proliferative, and anti-angiogenic compounds that modify signal transduction through the LPA signaling pathway. (C) 2009 Elsevier Inc. All rights reserved.
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