The role of perivascular macrophages in breast cancer metastasis.1. SPECIFIC OBJECTIVES The solid tumor microenvironment is composed of both malignant and non-malignant cells, and a growing body of evidence suggests that the fate of malignant cells can potentially be altered by the behavior of surrounding non-malignant cells. It is becoming increasingly clear that modulation of the tumor microenvironment has an important role to play in tumors displaying their full neoplastic potential and therefore targeting surrounding non-malignant cells, particularly immune cells, as potential therapeutic targets is not unheard of . Over the last decade the general concept of tumor development has seen a major change in relation to immune cells. New functions involving immune cells such as protumor cells have come to the fore. The immune subgroup usually implicated in this behavior is the tumor macrophage population. Clinical studies suggest that in nearly 80% of solid tumors, the presence of high numbers of macrophages is associated with disease progression and a poor prognosis. The tumor microenvironment has been shown to educate infiltrating monocytes to play supportive roles in tumor development and metastasis. But the macrophage population within a tumor microenvironment is quite heterogeneous, and not much is known about the role of various macrophage subsets in tumor cell spread and metastasis. Our laboratory has generated a transgenic mouse strain that allows the identification of a unique subpopulation of tissue-resident macrophages located in the perivascular space along venules and post-capillary lymphatics (hereafter referred to as perivascular macrophages; PVMs) ( Fig. 1 ). We have... half the paper... Amely PVM. The availability of a transgenic mouse strain that facilitates identification of PVM in combination with cutting-edge imaging technology puts us in an ideal position to gain new insights into this subset of innate immune cells. Furthermore, we believe that our experiments will improve knowledge of the contributions of m to the regulation of tumor immunology. References:1 Chechlinska, M et al. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nature reviews. Cancer 10, 2-3, (2010).2 Pollard, JW Tumor-educated macrophages promote tumor progression and metastasis. Nature reviews. Cancer 4, 71-78, (2004).3 Wyckoff, JB et al. Direct visualization of macrophage-assisted tumor cell intravasation in breast tumors. Cancer research 67, 2649-2656, (2007).
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