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Exosomes isolated from metabolically unhealthy normal weight and overweight phenotypes deteriorate the ER/PR positive breast cancer behavior

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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.

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Data Availability

Data are available from the authors upon reasonable request and with permission of the corresponding author.

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Funding

The present paper is derived from a Ph.D. thesis with no. 1401236855642 which received support from the Tehran University of Medical Sciences, Tehran, Iran.

Author information

Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Fataneh Esmaeili, Shadi Sadat Seyyed Ebrahimi, Solaleh Emamgholipour & Maliheh Paknejad

  2. Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Fataneh Esmaeili

  3. Cardiac primary prevention research center, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Abolhasani

  4. Cardiovascular diseases research center, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Abolhasani

  5. Department of General Surgery, School of Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Hossein Zabihi-Mahmoudabadi

  6. Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Solaleh Emamgholipour

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  1. Fataneh Esmaeili
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Contributions

FE performed experimental tests. FE, MP, and SE participated in the study design, interpreted results, and wrote the draft of the manuscript. MA and HZM conducted sample collection. MP and SE critically revised and edited the manuscript. SS helped with methodology and statistical analysis. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Solaleh Emamgholipour or Maliheh Paknejad.

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Ethics approval and consent to participate

The study protocol has been approved by the ethics committee of Tehran University of Medical Sciences (TUMS) with the following identification: IR. TUMS.MEDICINE. REC.1400.106). Every participant received comprehensive information regarding the study protocol and willingly provided written informed consent before their inclusion in the study.

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The authors declare that they have no conflict of interest.

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Esmaeili, F., Abolhasani, M., Zabihi-Mahmoudabadi, H. et al. Exosomes isolated from metabolically unhealthy normal weight and overweight phenotypes deteriorate the ER/PR positive breast cancer behavior. J Diabetes Metab Disord 23, 533–544 (2024). https://doi.org/10.1007/s40200-023-01295-1

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