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Mast cells in breast cancer angiogenesis

https://doi.org/10.1016/j.critrevonc.2017.04.009Get rights and content

Abstract

Mast cells, accumulate in the stroma surrounding certain tumors and take part to the inflammatory reaction occurring at the periphery of the tumor. Mast cell-secreted angiogenic cytokines facilitate tumor vascularization not only by a direct effect but also by stimulating other inflammatory cells of the tumor microenvironment to release other angiogenic mediators. An increased number of mast cells have been demonstrated in angiogenesis associated with solid tumors, including breast cancer. Mast cells might act as a new target for the adjuvant treatment of breast cancer through the selective inhibition of angiogenesis, tissue remodeling and tumor promoting molecules, allowing the secretion of cytotoxic cytokines and preventing mast cell mediated immune-suppression.

Section snippets

Mast cells and tumor growth

Since the early studies of Paul Ehrlich, who first made the observation that they often are localized around tumor masses (Ehrlich, 2013), mast cells have been associated either with resistance or susceptibility to tumors. Mast cells, indeed, accumulate in the stroma surrounding certain tumors and take part to the inflammatory reaction occurring at the periphery of the tumor. Mast cells can participate to tumor rejection by producing molecules like interleukin-1, -4, -6 (IL-1, IL-4, IL-6) and

Mast cells and angiogenesis in breast cancer

Breast cancer remains one of the most controversial malignancy. Despite of the fact that conventional histopathology was completed with an accurate molecular stratification, no significant improvement in prognosis and patient survival has been reported. These evidences suggested that additional factors influencing malignant progression would exist.

Increased vascularity has been shown in mammary ductal carcinoma in situ (Fig. 1) (Lee et al., 1997, Guidi et al., 1994), and highly vascular tumors

Therapeutic approach

There is clear evidence that mast cells play an active and coordinate role in enhancing tumor angiogenesis, either directly through the release of angiogenic cytokines and proteolytic enzymes, or indirectly through paracrine signals. Their biological activity may be in the same time synergic and compensatory in the tumor context and identification and targeting of both mast cells represents an attractive therapeutic approach in cancer. Inhibitors of mast cell function may prove therapeutically

Acknowledgements

This study was supported by a grant from “Associazione Italiana Mastocitosi”, and by the Grant “Traslocazione del gene Bcl6 nel carcinoma della mammella from “Ricerca Corrente 2016- IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy” to Domenico Ribatti.

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