Altered glycosylation of glycolipids, glycoproteins, or proteoglycans are frequently observed in tumor tissues and cultured cancer cell lines. These changes have diagnostic use but also can contribute to the ability of tumor cells to grow, induce neovascularization, metastasize, and avoid host immune surveillance. We are primarily intereseted in sulfated glycoconjugates and their interaction with extracellular matrix and cell surface adhesion molecules. These include thrombospondin, laminin, selectins, and apolipoprotein E. Human small cell lung carcinoma cell lines are used to examine expression and function of novel sulfated glycolipids. These glycolipids interact with thrombospondin and contribute to adhesion of SCLC cells on a thrombospondin matrix. Sulfated glycolipids on these cells are also being examined as potential ligands for selectin-mediated adhesion of SCLC cells to activated endothelium. Heparin oligosaccharides are being used to define the molecular basis for interactions of heparin and heparan sulfate proteoglycans with two binding motifs on the thrombospondin molecule and on a second heparin-binding protein, apolipoprotein E. Inhibitors of these interactions are being tested for effects on angiogenesis and tumor growth.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC009174-08
Application #
2464499
Study Section
Special Emphasis Panel (LP)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1996
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
MacDonald, Christopher J; Cheng, Robert Y S; Roberts, David D et al. (2009) Modulation of carcinogen metabolism by nitric oxide-aspirin 2 is associated with suppression of DNA damage and DNA adduct formation. J Biol Chem 284:22099-107
Isenberg, Jeff S; Qin, Yan; Maxhimer, Justin B et al. (2009) Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress. Matrix Biol 28:110-9
Ridnour, Lisa A; Thomas, Douglas D; Switzer, Christopher et al. (2008) Molecular mechanisms for discrete nitric oxide levels in cancer. Nitric Oxide 19:73-6
Isenberg, Jeff S; Frazier, William A; Krishna, Murali C et al. (2008) Enhancing cardiovascular dynamics by inhibition of thrombospondin-1/CD47 signaling. Curr Drug Targets 9:833-41
Kuznetsova, Svetlana A; Mahoney, David J; Martin-Manso, Gema et al. (2008) TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly. Matrix Biol 27:201-10
Isenberg, J S; Frazier, W A; Roberts, D D (2008) Thrombospondin-1: a physiological regulator of nitric oxide signaling. Cell Mol Life Sci 65:728-42
Ptaszynska, Malgorzata M; Pendrak, Michael L; Bandle, Russell W et al. (2008) Positive feedback between vascular endothelial growth factor-A and autotaxin in ovarian cancer cells. Mol Cancer Res 6:352-63
Isenberg, Jeff S; Maxhimer, Justin B; Powers, Perlita et al. (2008) Treatment of liver ischemia-reperfusion injury by limiting thrombospondin-1/CD47 signaling. Surgery 144:752-61
Isenberg, Jeff S; Romeo, Martin J; Maxhimer, Justin B et al. (2008) Gene silencing of CD47 and antibody ligation of thrombospondin-1 enhance ischemic tissue survival in a porcine model: implications for human disease. Ann Surg 247:860-8
Roberts, D D (2008) Thrombospondins: from structure to therapeutics. Cell Mol Life Sci 65:669-71

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