Adipose-Derived Stem Cells from Fat Tissue of Breast Cancer Microenvironment Present Altered Adipogenic Differentiation Capabilities

Federica Rey; Elena Lesma; Daniela Massihnia; Emilio Ciusani; Sara Nava; Chiara Vasco; Ghina Al Haj; Giorgio Ghilardi; Enrico Opocher; Alfredo Gorio; Stephana Carelli; Anna Maria Di Giulio

doi:10.1155/2019/1480314

Adipose-Derived Stem Cells from Fat Tissue of Breast Cancer Microenvironment Present Altered Adipogenic Differentiation Capabilities

Stem Cells Int. 2019 Aug 14:2019:1480314. doi: 10.1155/2019/1480314. eCollection 2019.

Authors

Federica Rey¹, Elena Lesma¹, Daniela Massihnia^{1

2}, Emilio Ciusani³, Sara Nava⁴, Chiara Vasco¹, Ghina Al Haj¹, Giorgio Ghilardi⁵, Enrico Opocher⁶, Alfredo Gorio¹, Stephana Carelli^{1

2}, Anna Maria Di Giulio^{1

2}

Affiliations

¹ Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
² Pediatric Clinical Research Center "Fondazione Romeo e Enrica Invernizzi", University of Milan, 20142 Milan, Italy.
³ Laboratory of Clinical Pathology and Medical Genetic, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
⁴ Cell Therapy Production Unit, Laboratory of Cellular Neurobiology, Cerebrovascular Unit, and Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁵ Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy.
⁶ General Surgery Unit, Department of Health Sciences, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into multiple cell types, including adipocytes, osteoblasts, and chondrocytes. The role of adipose-derived stem cells (ADSCs) in cancers is significantly relevant. They seem to be involved in the promotion of tumour development and progression and relapse processes. For this reason, investigating the effects of breast cancer microenvironment on ADSCs is of high importance in order to understand the relationship between tumour cells and the surrounding stromal cells. With the current study, we aimed to investigate the specific characteristics of human ADSCs isolated from the adipose tissue of breast tumour patients. We compared ADSCs obtained from periumbilical fat (PF) of controls with ADSCs obtained from adipose tissue of breast cancer- (BC-) bearing patients. We analysed the surface antigens and the adipogenic differentiation ability of both ADSC populations. C/EBPδ expression was increased in PF and BC ADSCs induced to differentiate compared to the control while PPARγ and FABP4 expressions were enhanced only in PF ADSCs. Conversely, adiponectin expression was reduced in PF-differentiated ADSCs while it was slightly increased in differentiated BC ADSCs. By means of Oil Red O staining, we further observed an impaired differentiation capability of BC ADSCs. To investigate this aspect more in depth, we evaluated the effect of selective PPARγ activation and nutritional supplementation on the differentiation efficiency of BC ADSCs, noting that it was only with a strong differentiation stimuli that the process took place. Furthermore, we observed no response in BC ADSCs to the PPARγ inhibitor T0070907, showing an impaired activation of this receptor in adipose cells surrounding the breast cancer microenvironment. In conclusion, our study shows an impaired adipogenic differentiation capability in BC ADSCs. This suggests that the tumour microenvironment plays a key role in the modulation of the adipose microenvironment located in the surrounding tissue.