Exosomes Isolated From Metabolically Unhealthy Normal Weight and Overweight Phenotypes Deteriorate the Er/Pr Positive Breast Cancer Behavior Publisher



Esmaeili F^{1, 2} ; Abolhasani M^{3, 4} ; Zabihimahmoudabadi H⁵ ; Seyyed Ebrahimi SS¹ ; Emamgholipour S^{1, 6} ; Paknejad M¹
Source: Journal of Diabetes and Metabolic Disorders Published:2023

Abstract

Purpose: Obesity has been linked to a higher risk of postmenopausal breast cancer Yet, research indicates an opposite correlation between obesity and premenopausal breast cancer risk. Various obesity phenotypes based on metabolic health could play a significant part. This study aims to assess how plasma exosomes taken from women with varying obesity phenotypes impact MCF-7 cell migration, matrix metalloproteinase-2 activity, and apoptosis. Methods: The characterization of isolated exosomes and their internalization into MCF-7 cells was evaluated. The treatment of MCF-7 cells with exosomes isolated from different groups was done. Migration, the activity of MMP-2, mRNA expression of Bax and Bcl-2, protein expression of p-53 and Thr55 p-p53, and apoptosis were assessed. Results: Isolated exosomes from unhealthy obese individuals increase MCF-7 cell migration. Regarding MMP activities, unhealthy normal weight and overweight and healthy obese groups isolated exosomes increase the MMP-2 activity than the treated group with exosomes isolated from counterpart groups. Furthermore, unhealthy normal weight and overweight and healthy obese obtained exosomes decrease apoptosis compared to counterpart groups. Conclusion: Altogether, plasma exosomes derived from both unhealthy individuals with normal weight and overweight status, as well as those with unhealthy obesity, negatively impacted the behavior of estrogen/progesterone receptor-positive breast cancer cells. © 2023, The Author(s), under exclusive licence to Tehran University of Medical Sciences.