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

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2023 Feb 11
PMID 36769251
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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.

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References
1.
Leng C, Zhang Z, Chen W, Luo H, Song J, Dong W . An integrin beta4-EGFR unit promotes hepatocellular carcinoma lung metastases by enhancing anchorage independence through activation of FAK-AKT pathway. Cancer Lett. 2016; 376(1):188-96. DOI: 10.1016/j.canlet.2016.03.023. View

2.
Vogetseder A, Thies S, Ingold B, Roth P, Weller M, Schraml P . αv-Integrin isoform expression in primary human tumors and brain metastases. Int J Cancer. 2013; 133(10):2362-71. DOI: 10.1002/ijc.28267. View

3.
Ricono J, Huang M, Barnes L, Lau S, Weis S, Schlaepfer D . Specific cross-talk between epidermal growth factor receptor and integrin alphavbeta5 promotes carcinoma cell invasion and metastasis. Cancer Res. 2009; 69(4):1383-91. PMC: 2741736. DOI: 10.1158/0008-5472.CAN-08-3612. View

4.
Huang R, Rofstad E . Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma. J Exp Clin Cancer Res. 2018; 37(1):92. PMC: 5924434. DOI: 10.1186/s13046-018-0763-x. View

5.
Liu X, Li J, Cadilha B, Markota A, Voigt C, Huang Z . Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis. Sci Adv. 2019; 5(6):eaav4275. PMC: 6584608. DOI: 10.1126/sciadv.aav4275. View