Startseite Medizin Local adipocyte cancer cell paracrine loop: can “sick fat” be more detrimental?
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Local adipocyte cancer cell paracrine loop: can “sick fat” be more detrimental?

  • Marie-Christine Rio EMAIL logo , Nassim Dali-Youcef und Catherine Tomasetto
Veröffentlicht/Copyright: 6. März 2015
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Abstract

This review article focuses on the emerging role of tumor resident adipocytes. It provides in vitro and in vivo evidence that they are essential for cancer development/progression. In addition to systemic effects, their tumor-promoting impact is dependent on local functions, notably via a complex adipocyte cancer cell paracrine loop (ACCPL). Indeed, this event leads to dramatic phenotypic and/or functional modifications of both cell types as well as of the extracellular matrix. Adipocytes undergo delipidation leading to adipocytes/cancer-associated adipocytes/cancer-associated fibroblasts de-differentiation processes. In turn, cancer cell aggressiveness is exacerbated through increased proliferation, migration, and invasion properties. This is accompanied by intense tissue remodeling, conducting to the occurrence of the tumor stroma. The molecular pathways involved in ACCPL remain largely unknown. Nevertheless, several clues are starting to emerge. Moreover, obesity is currently a sign of increased risk and poor prognosis in human carcinomas. How adiposopathy might impact tumors and specifically the ACCPL is still under investigation. However, available experimental, epidemiological, and clinical data allow to draw some directions. Interestingly, there are numerous similarities between the ACCPL-induced and obesity-related molecular alterations. It might, therefore, be hypothesized that obesity provides a “constitutively active” local permissive environment for cancer cells. Improving our knowledge about ACCPL in both lean and obese patients remains a challenging task. Indeed, deciphering the cellular and molecular mechanisms behind ACCPL might provide new targets for improving diagnosis/prognosis and the design of innovative therapeutic strategies, and even, in case of obesity, for preventing cancer.


Corresponding author: Marie-Christine Rio, Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U964, Université de Strasbourg, 1 rue L Fries, B.P. 10142, 67404 Illkirch Cedex, France, Phone: +44-038-865-3424, Fax: +44-038-865-3201, E-mail: . Web: http://www-igbmc.fr; and Equipe Labellisée Ligue contre le Cancer 2013, France

Acknowledgments

We thank Susan Chan for helpful discussions. This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Association pour la Recherche sur le Cancer, the Institut National du Cancer (PL-BIO ADIPOK 2011–2013), and the Ligue Nationale Française contre le Cancer (Equipe Labellisée 2013; Comités du Haut-Rhin et du Bas-Rhin). There is no a conflict of interest.

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Received: 2014-12-22
Accepted: 2015-1-28
Published Online: 2015-3-6
Published in Print: 2015-1-1

©2015 by De Gruyter

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