The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

Armignacco, Roberta; Cantini, Giulia; Poli, Giada; Guasti, Daniele; Nesi, Gabriella; Romagnoli, Paolo; Mannelli, Massimo; Luconi, Michaela

doi:10.3390/cancers11121931

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The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

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^1,†,

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Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy

Histology & Embryology Unit, Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy

Division of Pathological Anatomy, Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy

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Istituto Nazionale Biostrutture e Biosistemi (INBB), viale delle Medaglie d’Oro 305, 00136 Rome, Italy

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cancers 2019, 11(12), 1931; https://doi.org/10.3390/cancers11121931

Received: 9 November 2019 / Revised: 26 November 2019 / Accepted: 27 November 2019 / Published: 4 December 2019

(This article belongs to the Special Issue Adrenocortical Carcinoma)

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Abstract

Metabolic interplay between the tumor microenvironment and cancer cells is a potential target for novel anti-cancer approaches. Among stromal components, adipocytes and adipose precursors have been shown to actively participate in tumor progression in several solid malignancies. In adrenocortical carcinoma (ACC), a rare endocrine neoplasia with a poor prognosis, cancer cells often infiltrate the fat mass surrounding the adrenal organ, enabling possible crosstalk with the adipose cells. Here, by using an in vitro co-culture system, we show that the interaction between adipose-derived stem cells (ASCs) and the adrenocortical cancer cell line H295R leads to metabolic and functional reprogramming of both cell types: cancer cells limit differentiation and increase proliferation of ASCs, which in turn support tumor growth and invasion. This effect associates with a shift from the paracrine cancer-promoting IGF2 axis towards an ASC-associated leptin axis, along with a shift in the SDF-1 axis towards CXCR7 expression in H295R cells. In conclusion, our findings suggest that adipose precursors, as pivotal components of the ACC microenvironment, promote cancer cell reprogramming and invasion, opening new perspectives for the development of more effective therapeutic approaches. View Full-Text

Keywords: adipose precursors; adipogenesis; invasion; cancer; cell reprogramming; leptin

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MDPI and ACS Style

Armignacco, R.; Cantini, G.; Poli, G.; Guasti, D.; Nesi, G.; Romagnoli, P.; Mannelli, M.; Luconi, M. The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model. Cancers 2019, 11, 1931. https://doi.org/10.3390/cancers11121931

AMA Style

Armignacco R, Cantini G, Poli G, Guasti D, Nesi G, Romagnoli P, Mannelli M, Luconi M. The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model. Cancers. 2019; 11(12):1931. https://doi.org/10.3390/cancers11121931

Chicago/Turabian Style

Armignacco, Roberta, Giulia Cantini, Giada Poli, Daniele Guasti, Gabriella Nesi, Paolo Romagnoli, Massimo Mannelli, and Michaela Luconi. 2019. "The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model" Cancers 11, no. 12: 1931. https://doi.org/10.3390/cancers11121931

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The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

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