The long-term objective is to understand the role of adhesion molecules in the pathogenesis of non-Hodgkin's lymphomas. The proposed research focuses on the expression and function of adhesion molecules from patients with different cell types and stages of lymphomas. The profile of cell surface adhesion molecules on lymphoma cells will be established by use of a panel of monoclonal antibodies specific for different adhesion proteins. Adhesion inducing or blocking reagents such as monoclonal antibodies or pharmacologic reagents will be used to determine the functional capacity of cellular adhesion molecules in a variety of adhesion assays such as lymphoma cell adhesion to vascular endothelial and bone marrow stromal cells, extracellular matrix components, and other lymphoma cells. In addition, the hypothesis that serum levels of soluble adhesion molecules may correlate with disease stage or tumor burden will be tested. Serum from normal individuals and patients will be measured and compared by competitive inhibition assays or by a quantitative ELISA. From the foundation of data obtained from the analysis of lymphoma-associated adhesion molecules, a comprehensive definition of the adhesion molecules that delineate discrete stages of non-Hodgkin's lymphomas may be determined. These markers will be correlated with patient tumor burden and relapse to determine whether serum levels of soluble adhesion molecules reflect clinical stage at presentation and clinical outcome, and thus may also be used to monitor patient response to therapy. Ultimately, the identification of lymphoma indicative cell adhesion molecules should allow the development of rational approaches for devising new diagnostic tests and therapeutic regimens as well as to initiate mechanistic studies concerning organ localization, cell recirculation, positive and negative proliferation signals, and immune system evasion.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA062596-02
Application #
2103955
Study Section
Special Emphasis Panel (SRC (57))
Project Start
1993-09-01
Project End
1997-06-30
Budget Start
1994-09-01
Budget End
1995-06-30
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Diaz-Montero, C Marcela; Wygant, James N; McIntyre, Bradley W (2006) PI3-K/Akt-mediated anoikis resistance of human osteosarcoma cells requires Src activation. Eur J Cancer 42:1491-500
Diaz-Montero, C Marcela; McIntyre, Bradley W (2005) Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents. BMC Cancer 5:39
Qin, Chunlin; Brunn, Jan C; Baba, Otto et al. (2003) Dentin sialoprotein isoforms: detection and characterization of a high molecular weight dentin sialoprotein. Eur J Oral Sci 111:235-42
Marco, Rex A W; Diaz-Montero, C Marcela; Wygant, James N et al. (2003) Alpha 4 integrin increases anoikis of human osteosarcoma cells. J Cell Biochem 88:1038-47
Miyamoto, Yuko J; Mitchell, Jason S; McIntyre, Bradley W (2003) Physical association and functional interaction between beta1 integrin and CD98 on human T lymphocytes. Mol Immunol 39:739-51
Woodside, Darren G; Wooten, David K; Teague, T Kent et al. (2003) Control of T lymphocyte morphology by the GTPase Rho. BMC Cell Biol 4:2
Diaz-Montero, C M; McIntyre, B W (2003) Acquisition of anoikis resistance in human osteosarcoma cells. Eur J Cancer 39:2395-402
Lee, Lawrence Y; Miyamoto, Yuko J; McIntyre, Bradley W et al. (2002) The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell-mediated responses. J Clin Invest 110:1461-71
Mitchell, Jason S; Kanca, Oguz; McIntyre, Bradley W (2002) Lipid microdomain clustering induces a redistribution of antigen recognition and adhesion molecules on human T lymphocytes. J Immunol 168:2737-44
Caruso, D A; McIntyre, B W (2001) In an adhesion dependent human gastric adenocarcinoma cell line, integrin ligation without adhesion rescues from anoikis but is not sufficient for cell cycle progression. Cell Death Differ 8:665-78

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