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Mechanisms of Disease: adipokines and breast cancer—endocrine and paracrine mechanisms that connect adiposity and breast cancer

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 345–354 (2007)Cite this article

Abstract

A vast number of epidemiological studies suggest an important, but still controversial, role for obesity and adipose tissue mass in breast cancer risk and an association with tumor phenotype. The main conclusions from these studies raise the possibility that the adipose tissue can act as an effector organ that influences both cancer risk and tumor behavior. Here we also review heterotypic mechanisms in breast-cancer tumorigenesis; these mechanisms involve soluble secreted factors from peritumoral cells, extracellular-matrix components and interactions between stromal cells and tumor cells that create a specific and local peritumoral microenvironment. As a special focus, we discuss the increasing evidence for a role of peritumoral adipose tissue and secreted adipokines (such as adiponectin and leptin) in breast cancer; furthermore, the cellular and molecular basis of the peritumoral 'desmoplastic' tissue reaction observed in breast cancer is reviewed in detail.

Key Points

  • Peritumoral adipose tissue is involved in multiple heterotypic signaling mechanisms, such as secretion of extracellular matrix components and soluble factors from peritumoral adipocytes and interactions between stromal cells and tumor cells

  • Leptin and adiponectin are adiponectins secreted by adipocytes; these adipokines have endocrine and paracrine effects and both regulate mammary epithelial cell behavior and can influence tumor growth and progression

  • The molecular basis of the desmoplastic tissue reaction observed in breast cancer involves tumor necrosis factor, interleukin 11 and matrix metalloproteinase 11, which lead to a local inhibition of adipocyte differentiation

  • Peritumoral adipose tissue and locally produced adipokines could provide future therapeutic targets for breast cancer

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Figure 1: Leptin activates proliferation and cell survival whereas adiponectin inhibits proliferation in mammary epithelial cells
Figure 2: The role of the adipokines leptin and adiponectin in breast cancer biology
Figure 3: Regulation of the adipokines leptin and adiponectin in breast cancer
Figure 4: The desmoplastic tissue reaction in breast cancer
Figure 5: Molecular and cellular pathogenesis of the peritumoral desmoplastic tissue reaction in breast cancer

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Authors and Affiliations

  1. J Schölmerich is Professor and Director of the Department, in the Department of Internal Medicine I, A Schäffler is an Assistant Professor, and C Buechler is an Assistant Professor and molecular biologist, University of Regensburg, Germany.,

    Andreas Schäffler, Jürgen Schölmerich & Christa Buechler

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  1. Andreas Schäffler
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  2. Jürgen Schölmerich
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  3. Christa Buechler
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Correspondence to Andreas Schäffler.

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Schäffler, A., Schölmerich, J. & Buechler, C. Mechanisms of Disease: adipokines and breast cancer—endocrine and paracrine mechanisms that connect adiposity and breast cancer. Nat Rev Endocrinol 3, 345–354 (2007). https://doi.org/10.1038/ncpendmet0456

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