Korean J Physiol Pharmacol 2023; 27(2): 157-165
Published online March 1, 2023 https://doi.org/10.4196/kjpp.2023.27.2.157
Copyright © Korean J Physiol Pharmacol.
Lei Qiao1, Chao Dong1, Jiaojiao Zhang2, and Gang Sun1,*
Departments of 1Breast and Thyroid Surgery, 2Anesthesia and Perioperative Medicine, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang Province 830000, China
Correspondence to:Gang Sun
Author contributions: L.Q. designed the experiments, and C.D. conducted the experiments. J.Z. analyzed and interpreted the data. G.S. prepared the manuscript with contributions from all coauthors.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and current therapeutic strategies are limited in their effectiveness. The expressions of Rab5 and the M2 tumor-associated macrophage marker CD163 in tissues were detected by Western blot. The migration and invasion of cells were determined using a Transwell assay. The expressions of the exosome markers were evaluated by Western blot. The polarization of human macrophages (THP-1) was determined by incubation of THP-1 cells with conditioned medium or exosomes collected from MDA-MB-231 cells with indicated transfections or by a coculture system of THP-1 and MDA-MB-231 cells. The M1 and M2 macrophage markers were evaluated by qRT-PCR. The expression of Rab5 in TNBC was significantly higher than that in normal breast tissue. Rab5 expressions in triple-negative and luminal A breast cancer were higher than those in other molecular subtypes. Higher CD163 expression was observed in triple-negative breast cancer and in triple-negative and luminal B subtypes. Rab5 knockdown suppressed but Rab5 overexpression promoted the migration and invasion capacity of MDA-MB-231 cells. The levels of CD63 and CD9 in the medium of Rab5 knockdown cells were lower than those in control cells, whereas higher levels of CD63 and CD9 were observed in Rab5 overexpression cells. Rab5 knockdown decreased the excretion but did not alter the diameter of the exosomes. Knockdown of Rab5 facilitated the anti-tumor polarization of macrophages, which was partially reversed by Rab5 overexpression. Therefore, Rab5 is expected to be a potential therapeutic target for triple-negative breast cancer.
Keywords: Exosomes, Rab5 GTP-binding proteins, Triple-negative breast cancer, Tumor-associated macrophages
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