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The role of Perivascular Macrophages in Breast Cancer Metastasis

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The role of Perivascular Macrophages in Breast Cancer Metastasis.

1. SPECIFIC AIMS

The solid tumor microenvironment is comprised of both malignant and non-malignant cells and an increasing body of evidence suggests that the fate of malignant cells can potentially be altered by the behavior of the surrounding non-malignant cells. It is becoming increasingly evident that the modulation of tumor microenvironment has an important role to play in tumors displaying their full neoplastic potential and thus targeting the surrounding non-malignant cells particularly the immune cells as potential therapeutic targets is not unheard of. In the last decade the general concept for tumour development has seen a large shift in relation to immune cells. Novel functions implicating immune cells as protumoral have come to the forefront. The immune subset that is usually implicated in this behavior is the tumor macrophage population. Clinical studies suggest that in almost 80% of the solid tumors, the presence of elevated macrophage numbers is associated with disease progression and poor prognosis. The tumor microenvironment has been shown to educate the infiltrating monocytes to perform roles that are supportive of tumor development and metastasis. But the macrophage population within a tumor microenvironment is quite heterogenous and not much is known about the role of various macrophage subsets in tumor cell dissemination and metastasis. Our laboratory has generated a transgenic mouse strain that allows for the identification of a unique subpopulation of tissue resident macrophages localising in the perivascular space along the post-capillary venules and lymphatics (hereafter referred to as perivascular macrophages; PVM) (Fig. 1). We have sho...

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...amely PVM. The availability of a transgenic mouse strain that facilitates the identification of PVM in combination with cutting edge imaging technology puts us in an ideal position to obtain novel information on this innate immune cell subset. In addition, we believe that our experiments will increase the knowledge of the contributions of m to the regulation of tumour-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, J. W. Tumour-educated macrophages promote tumour progression and metastasis. Nature reviews. Cancer 4, 71-78, (2004).

3 Wyckoff, J. B. et al. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer research 67, 2649-2656, (2007).
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