Integrin profile of circulating tumour cells in breast cancer patients

Background. Integrins, as adhesion molecules, play a key role in the interaction of cells with the basal membrane and intercellular matrix. Numerous studies demonstrate evidence of increased expression of integrins on tumor cells in different types of cancer. Thus, β3 and αV integrins are associated...

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Main Authors: E. S. Grigoryeva, L. A. Tashireva, V. V. Alifanov, M. V. Zavyalova, V. M. Perelmuter
Format: Article
Language:Russian
Published: Russian Academy of Sciences, Tomsk National Research Medical Center 2024-09-01
Series:Сибирский онкологический журнал
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Online Access:https://www.siboncoj.ru/jour/article/view/3195
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author E. S. Grigoryeva
L. A. Tashireva
V. V. Alifanov
M. V. Zavyalova
V. M. Perelmuter
author_facet E. S. Grigoryeva
L. A. Tashireva
V. V. Alifanov
M. V. Zavyalova
V. M. Perelmuter
author_sort E. S. Grigoryeva
collection DOAJ
description Background. Integrins, as adhesion molecules, play a key role in the interaction of cells with the basal membrane and intercellular matrix. Numerous studies demonstrate evidence of increased expression of integrins on tumor cells in different types of cancer. Thus, β3 and αV integrins are associated with stem-like features of tumor cells, and β4 integrin as α6β4 heterodimer provides anchorage-independent survival of malignant mammary epithelial cells. However, all the described functions of integrins have been investigated exclusively on primary tumor cells. The functional significance and expression pattern of integrins on circulating tumor cells (CTCs) remains unclear. The aim of the study was to evaluate the β3, β4 and αvβ5 integrin expression on CTCs and its association with molecular subtype, stage and lymph node metastasis in breast cancer patients Material and Methods. The study included 22 patients with T1–4N0–3M0 invasive ductal breast carcinoma. Venous blood was taken from patients without neoadjuvant chemotherapy (group 1) and after neoadjuvant chemotherapy (group 2) in the volume of 12 ml into vacuum tubes with EDTA. The expression of CTC integrins including stemness features CD44/CD24, CD133 and ALDH1, and epithelial-mesenchymal transition (EMT) (N-cadherin) was evaluated by flow cytometry. Results. CTCs with β3+β4-αvβ5- and β3-β4+αvβ5+ phenotypes and stemness properties were associated with larger tumor size (T4) in breast cancer patients. The β3 integrin expression was associated with more aggressive molecular subtypes of breast cancer. Administration of neoadjuvant chemotherapy did not affect the expression pattern of β3, β4 and αvβ5 integrins in CTCs. Conclusion. In breast cancer, most CTCs expressed β3, β4 and αvβ5 integrins despite the lack of attachment to the basal membrane and intercellular matrix. The expression of the above integrins on CTCs was associated with breast cancer molecular subtype, stage and lymph node metastasis, and therefore its evaluation can be considered as one of the objectives of liquid biopsy study.
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spelling doaj-art-48aff8485a4f4bcca69b5a04604f03cb2025-08-20T03:18:24ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682024-09-01234869510.21294/1814-4861-2024-23-4-86-951255Integrin profile of circulating tumour cells in breast cancer patientsE. S. Grigoryeva0L. A. Tashireva1V. V. Alifanov2M. V. Zavyalova3V. M. Perelmuter4Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesBackground. Integrins, as adhesion molecules, play a key role in the interaction of cells with the basal membrane and intercellular matrix. Numerous studies demonstrate evidence of increased expression of integrins on tumor cells in different types of cancer. Thus, β3 and αV integrins are associated with stem-like features of tumor cells, and β4 integrin as α6β4 heterodimer provides anchorage-independent survival of malignant mammary epithelial cells. However, all the described functions of integrins have been investigated exclusively on primary tumor cells. The functional significance and expression pattern of integrins on circulating tumor cells (CTCs) remains unclear. The aim of the study was to evaluate the β3, β4 and αvβ5 integrin expression on CTCs and its association with molecular subtype, stage and lymph node metastasis in breast cancer patients Material and Methods. The study included 22 patients with T1–4N0–3M0 invasive ductal breast carcinoma. Venous blood was taken from patients without neoadjuvant chemotherapy (group 1) and after neoadjuvant chemotherapy (group 2) in the volume of 12 ml into vacuum tubes with EDTA. The expression of CTC integrins including stemness features CD44/CD24, CD133 and ALDH1, and epithelial-mesenchymal transition (EMT) (N-cadherin) was evaluated by flow cytometry. Results. CTCs with β3+β4-αvβ5- and β3-β4+αvβ5+ phenotypes and stemness properties were associated with larger tumor size (T4) in breast cancer patients. The β3 integrin expression was associated with more aggressive molecular subtypes of breast cancer. Administration of neoadjuvant chemotherapy did not affect the expression pattern of β3, β4 and αvβ5 integrins in CTCs. Conclusion. In breast cancer, most CTCs expressed β3, β4 and αvβ5 integrins despite the lack of attachment to the basal membrane and intercellular matrix. The expression of the above integrins on CTCs was associated with breast cancer molecular subtype, stage and lymph node metastasis, and therefore its evaluation can be considered as one of the objectives of liquid biopsy study.https://www.siboncoj.ru/jour/article/view/3195breast cancercirculating tumor cellsintegrinsneoadjuvant chemotherapy
spellingShingle E. S. Grigoryeva
L. A. Tashireva
V. V. Alifanov
M. V. Zavyalova
V. M. Perelmuter
Integrin profile of circulating tumour cells in breast cancer patients
Сибирский онкологический журнал
breast cancer
circulating tumor cells
integrins
neoadjuvant chemotherapy
title Integrin profile of circulating tumour cells in breast cancer patients
title_full Integrin profile of circulating tumour cells in breast cancer patients
title_fullStr Integrin profile of circulating tumour cells in breast cancer patients
title_full_unstemmed Integrin profile of circulating tumour cells in breast cancer patients
title_short Integrin profile of circulating tumour cells in breast cancer patients
title_sort integrin profile of circulating tumour cells in breast cancer patients
topic breast cancer
circulating tumor cells
integrins
neoadjuvant chemotherapy
url https://www.siboncoj.ru/jour/article/view/3195
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AT latashireva integrinprofileofcirculatingtumourcellsinbreastcancerpatients
AT vvalifanov integrinprofileofcirculatingtumourcellsinbreastcancerpatients
AT mvzavyalova integrinprofileofcirculatingtumourcellsinbreastcancerpatients
AT vmperelmuter integrinprofileofcirculatingtumourcellsinbreastcancerpatients