Tumor microenvironment

Inflammatory mediators released by resident neutrophils and mast cells in solid tumors attract migrating monocytes, which differentiate into macrophages. Local chemokines and cytokines activate macrophages, which become phagocytic and release additional inflammatory mediators. When mice deficient in macrophages were crossed with mice predisposed to mammary cancer, the rate of tumor pro- 

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Chan N, Pires IM, Bencokova Z et al (2010) Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Cancer Res 70 8045-8054... 

Lin Q, Yun Z (2010) Impact of the hypoxic tumor microenvironment on the regulation of cancer stem ceU characteristics. Cancer Biol Ther 9 949-956... 

Celis, J.E., et al. (2004) Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics. 3, 327 4. 

Gordon et al. (48) recently performed a pathway-based pharmacogenomic study on rectal cancer treated with chemoradiation in which they evaluated 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression (drug metabolism, tumor microenvironment, cell cycle control, and DNA repair). They applied the CART analysis and found that a classification tree with four genes (lL-8, lCAM-1, TGF-, and... 

One of the major features of solid tumors and even small deposits of tumor tissue is deficiency in the level of oxygen, because of an inadequate vascular supply. The adenosine elevation in response to hypoxia is not exclusive to tumor tissues, but, in this context, the adenosine elevation is localized to the tumor microenvironment, since the surrounding tissue is normally oxygenated. Adenosine is generated mainly by two enzymatic systems intra- or extracellularly localized 5 -nucleoti-dases and cytoplasmic S-adenosylhomocysteine hydrolase. The processes of adenosine elimination in the cell involve reactions catalyzed by adenosine deaminase and adenosine kinase (Shryock and Belardinelli 1997) yielding inosine or 5 -AMP,... 

Sloane BF, Yan S, Podgorski I et al (2005) Cathepsin B and tumor proteolysis contribution of the tumor microenvironment. Semin Cancer Biol 15 149-157... 

Ben-Baruch, A. (2003). Host microenvironment in breast cancer development Inflammatory cells, cytokines and chemokines in breast cancer progression Reciprocal tumor-microenvironment interactions. Breast Cancer Res. 5, 31-36. 

A number of animal model systems have been developed to provide tumor microenvironments that mimic the clinical situation. However, there are no perfect animal models for drug development. The adequacy of any specific animal model depends on its validity, selectivity, predictability, and reproducibility (22). In cancer chemotherapy, animal models are selected to simultaneously demonstrate antitumor efficacy and evaluate systemic toxicities in an intact organism. Ideally, the tumor system under study in the animal model should be genetically stable over time, with homogeneous characteristics that mimic human tumor biology. In oncology, a variety of diverse animal models for human tumors have been developed. These models can be broadly categorized in to three... 

Nicolson, G. L. (1994). Tumor microenvironment Paracrine and autocrine growth mechanisms and metastasis to specific sites. Front. Radiat. Then Oncol. 28, 11-24. 

Allinen M., Beroukhim R., Cai L., et al. (2004) Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell, 6, 17-32. 

Endothelins and their receptors may be induced within the tumor microenvironment by hypoxia via stabilization of HIF-la as well as by inflammatory cytokines and chemokines [44]. These studies imply that multiple factors within the tumor microenvironment upregulate endothelin expression in local tumor regions, which in turn induces CCR7 expression by tumor cells. Interestingly, another chemokine receptor (i.e., CXCR4) associated with cancer cells is also induced by hypoxia via HIF-1-dependent mechanisms [19], suggesting that hypoxia may be an inducer of a variety of chemokine receptors. (See Chapter 3.)... 

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