INTERACTION OF TUMOR AND HOST CELLS WITH ADHESION AND EXTRACELLULAR MATRIX MOLECULES IN THE DEVELOPMENT OF MULTIPLE MYELOMA

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• 作者：Gerrard Teoh ; MD^* ; Kenneth C. Anderson ; MD^*
• 刊名：Hematology/Oncology Clinics of North America
• 出版年：1997
• 出版时间：1 February 1997
• 年：1997
• 卷：11
• 期：1
• 页码：27-42
• 全文大小：1011 K

文摘

Adhesion molecules mediate functional interactions among cells, the extracellular matrix (ECM), and the extracellular fluid, and they play a central role in the normal immune response. Cell surface ¦Á₄¦Â₁ and ¦Á₅¦Â₁ integrins on natural killer (NK) cells, for example, bind to the ECM fibronectin and transduce signals intracellularly by induction of tyrosine phosphorylation of paxillin. The interaction of adhesion molecules with ligands on target cells may alter their cell surface phenotype and functional repertoire, including migration, cytokine secretion, and growth. Exogenous stimuli can similarly alter adhesion molecule expression and cellular function. For example, both hydroxy-3-nitrophenyl acetate and ezrin upregulate adhesion molecules on NK cells, and ezrin also enhances interleukin (IL)-2¨Cmediated NK cell killing. Finally, the functional significance of adhesion molecules is confirmed by clinical conditions that arise when they are lacking. For example, the ¡°leukocyte adhesion deficiencies?are characterized by recurrent severe infections in children and are either type 1, resulting from lack of lymphocyte function¨Cassociated antigen (LFA)-1 and Mac-1, or type 2, with deficiency of Sialyl-Lewis X ligand for E selectin.

In the setting of malignancies, adhesion molecules play a role in homotypic adhesion of tumor cells, as well as in tumor cell homing, local invasion, and distant metastases. In addition, the pattern of expression of adhesion molecules on tumor cells has been correlated with disease course and prognosis. For example, intercellular adhesion molecule (ICAM)-1 is expressed on hematologic malignancies, such as acute lymphoblastic leukemia (ALL) and Hodgkin""s disease (HD) cells, as well as on solid tumors, such as sarcoma. Increased expression of ICAM-1 correlates with stage of disease in HD as well as Ewing""s sarcoma, and with relapse in HD. Within multiple myeloma (MM), LFA-1 expression is correlated with tumor cell growth. Moreover, in MM as well as in B-cell chronic lymphocytic leukemia (CLL), tumor cells bearing adhesion molecules are correlated with advanced-stage disease and poor prognosis. In addition, different epitopes on adhesion molecules often mediate different biologic functions, and variations in their genetic and/or molecular structure may correlate with phenotypic variations of the tumor cell and disease course. In MM, for example, different CD44 splice variants define prognostic subgroups of patients. Finally, levels of circulating adhesion molecules in some cases have clinical importance. For example, serum neural cell adhesion molecule (eNCAM, CD56) expression is associated with malignant, rather than benign, paraproteinemia.