Chemokines and Cancer
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Humana, $125.00, 400 pp., 1999 ISBN 089603562X | ISBN: 0-896-03562-X
Tumor-associated leukocytes, and mononuclear phagocytes in particular, are discussed in several chapters. Opdenakker and van Damme give a detailed account of monocyte attractants that are produced by tumor cells, and present useful tables of human and murine chemokine genes and their expression in experimental tumors. Do mononuclear phagocytes protect the organism against tumors or do they favor tumor growth? The dilemma is discussed in detail by Rollins in a knowledgeable chapter on MCP-1 that goes back to studies published at the beginning of the century and also refers to the tumor-derived attractants and inhibitors, which were described in the 1970s and can be regarded as a prelude to chemokines. Mantovani and colleagues complement with a good overview Rollin's account. Conclusions? Tumor-associated macrophages may be good not only for the host but also for the tumor. MCP-1 has been used successfully to inhibit tumor growth in animal models. As pointed out by Rollins, MCP-1 may act by simply attracting monocytes (the hypothesis I tend to favor), whereas monocyte/macrophage activation may depend on other factors. MCP-1, however, could also work for the tumor, as the experts suggest; for example, by arresting the monocytes at the tumor boundary, and thus preventing infiltration, and by stimulating production of trophic factors. Mantovani, on the other hand, points out that chemokines may exert anti-tumor effects by recruiting dendritic cells and T lymphocytes. Another interesting, well-written contribution is that of Hamilton, who reviews possible mechanisms of immune-mediated inflammation and emphasizes the potential role of cytokines in concert with chemokines. The chapters on chemokine expression in certain tumors (ovarian and cervical cancer, gliomas and meningiomas) are useful examples of concrete situations. MCP-1 is often highly expressed in the tumors, which could indicate that its role is predominant in these pathologies. The picture may change, of course, as more and more chemokines are studied in tumor specimens. Strieter and colleagues have reported that CXC chemokines regulate angiogenesis and can consequently affect tumor growth. They summarize their theory that angiogenic and angiostatic effects of CXC chemokines depend on the presence or absence of the sequence Glu-Leu-Arg before the first cysteine. This view has not remained unchallenged and it is unfortunate that dissension is not discussed in the chapter. As pointed out by Mantovani, receptors for angiogenic or angiostatic chemokines have not been identified on endothelial cells and the mechanism for the described effects on angiogenesis is unknown.
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