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Cytokine networks in solid human tumors: regulation of angiogenesis
Author(s) -
Leek R.D.,
Harris A.L.,
Lewis C.E.
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.56.4.423
Subject(s) - stromal cell , angiogenesis , cytokine , biology , receptor , immune system , cancer research , cell type , tumor microenvironment , proinflammatory cytokine , microbiology and biotechnology , immunology , cell , inflammation , genetics
Abstract The isolation, purification, and molecular cloning of an increasing number of cytokines and their receptors have allowed major advances in our understanding of the relevance of these proteins to the pathobiology and treatment of such human diseases as neoplasia. Cytokines produced by the multiple cell types present within the microenvironment of solid tumors form a complex, dynamic network, in which they have overlapping properties, induce other cytokines and alter the expression of soluble and cell surface‐bound cytokine receptors. A broad number of such intratumoral cytokines have multiple effects on tumor progression. These include direct and indirect effects both on tumor cell growth and metastatic behaviors and on such cells in the stromal compartment as fibroblasts, infiltrating immune cells, and endothelial cells in the microvasculature. Here, we review the sites of production and multifaceted role of several key cytokines in the stimulation of a new blood supply within growing neoplasms. The clinical implications and new therapeutic targets suggested by this rapidly emerging picture of the cellular and molecular mechanisms subserving tumor angiogenesis are also discussed. J. Leukoc. Biol. 56: 423–435; 1994.