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Article

The Association of Integrins β3, β4, and αVβ5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients

by
Evgeniya S. Grigoryeva
1,2,*,
Luibov A. Tashireva
1,3,
Olga E. Savelieva
3,4,
Marina V. Zavyalova
3,
Nataliya O. Popova
5,
Gleb A. Kuznetsov
3,
Elena S. Andryuhova
3 and
Vladimir M. Perelmuter
3
1
The Laboratory of Molecular Therapy of Cancer, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
2
The Laboratory of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
3
The Department of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
4
Research Center, Saint-Petersburg State Pediatric Medical University, 194100 Saint-Petersburg, Russia
5
The Department of Chemotherapy, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(3), 2929; https://doi.org/10.3390/ijms24032929
Submission received: 9 November 2022 / Revised: 11 January 2023 / Accepted: 30 January 2023 / Published: 2 February 2023
(This article belongs to the Special Issue Circulating Tumor Cells: Pathological, Molecular and Functional Characteristics 3.0)
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Abstract

Integrins are cell adhesion receptors, which play a role in breast cancer invasion, angiogenesis, and metastasis. Moreover, it has been shown that exosomal integrins provide organotropic metastasis in a mouse model. In our study, we aimed to investigate the expression of integrins β3, β4, and αVβ5 on exosomes and tumor cells (circulating tumor cells and primary tumor) and their association with the localization of distant metastasis. We confirmed the association of exosomal integrin β4 with lung metastasis in breast cancer patients. However, we were unable to evaluate the role of integrin β3 in brain metastasis due to the rarity of this localization. We established no association of exosomal integrin αVβ5 with liver metastasis in our cohort of breast cancer patients. The further evaluation of β3, β4, and αVβ5 integrin expression on CTCs revealed an association of integrin β4 and αVβ5 with liver, but not the lung metastases. Integrin β4 in the primary tumor was associated with liver metastasis. Furthermore, an in-depth analysis of phenotypic characteristics of β4+ tumor cells revealed a significantly increased proportion of E-cadherin+ and CD44+CD24- cells in patients with liver metastases compared to patients with lung or no distant metastases.
Keywords: breast cancer; metastasis; circulating tumor cells; exosomes; integrin breast cancer; metastasis; circulating tumor cells; exosomes; integrin

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MDPI and ACS Style

Grigoryeva, E.S.; Tashireva, L.A.; Savelieva, O.E.; Zavyalova, M.V.; Popova, N.O.; Kuznetsov, G.A.; Andryuhova, E.S.; Perelmuter, V.M. The Association of Integrins β3, β4, and αVβ5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients. Int. J. Mol. Sci. 2023, 24, 2929. https://doi.org/10.3390/ijms24032929

AMA Style

Grigoryeva ES, Tashireva LA, Savelieva OE, Zavyalova MV, Popova NO, Kuznetsov GA, Andryuhova ES, Perelmuter VM. The Association of Integrins β3, β4, and αVβ5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients. International Journal of Molecular Sciences. 2023; 24(3):2929. https://doi.org/10.3390/ijms24032929

Chicago/Turabian Style

Grigoryeva, Evgeniya S., Luibov A. Tashireva, Olga E. Savelieva, Marina V. Zavyalova, Nataliya O. Popova, Gleb A. Kuznetsov, Elena S. Andryuhova, and Vladimir M. Perelmuter. 2023. "The Association of Integrins β3, β4, and αVβ5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients" International Journal of Molecular Sciences 24, no. 3: 2929. https://doi.org/10.3390/ijms24032929

APA Style

Grigoryeva, E. S., Tashireva, L. A., Savelieva, O. E., Zavyalova, M. V., Popova, N. O., Kuznetsov, G. A., Andryuhova, E. S., & Perelmuter, V. M. (2023). The Association of Integrins β3, β4, and αVβ5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients. International Journal of Molecular Sciences, 24(3), 2929. https://doi.org/10.3390/ijms24032929

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