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- Title
Extracellular vesicles derived from SARS-CoV-2 M-protein-induced triple negative breast cancer cells promoted the ability of tissue stem cells supporting cancer progression.
- Authors
Hoai-Nga Thi Nguyen; Cat-Khanh Vuong; Mizuho Fukushige; Momoko Usuda; Liora Kaho Takagi; Toshiharu Yamashita; Mana Obata-Yasuoka; Hiromi Hamada; Motoo Osaka; Toru Tsukada; Yuji Hiramatsu; Osamu Ohneda
- Abstract
Introduction: SARS-CoV-2 infection increases the risk of worse outcomes in cancer patients, including those with breast cancer. Our previous study reported that the SARS-CoV-2 membrane protein (M-protein) promotes the malignant transformation of triple-negative breast cancer cells (triple-negative BCC). Methods: In the present study, the effects of M-protein on the ability of extracellular vesicles (EV) derived from triple-negative BCC to regulate the functions of tissue stem cells facilitating the tumor microenvironment were examined. Results: Our results showed that EV derived from M-protein-induced triplenegative BCC (MpEV) significantly induced the paracrine effects of adipose tissuederived mesenchymal stem cells (ATMSC) on non-aggressive BCC, promoting the migration, stemness phenotypes, and in vivo metastasis of BCC, which is related to PGE2/IL1 signaling pathways, in comparison to EV derived from normal triplenegative BCC (nEV). In addition to ATMSC, the effects of MpEV on endothelial progenitor cells (EPC), another type of tissue stem cells, were examined. Our data suggested that EPC uptaking MpEV acquired a tumor endothelial cell-like phenotype, with increasing angiogenesis and the ability to support the aggressiveness and metastasis of non-aggressive BCC. Discussion: Taken together, our findings suggest the role of SARS-CoV-2M-protein in altering the cellular communication between cancer cells and other non-cancer cells inside the tumormicroenvironment via EV. Specifically, M-proteins induced the ability of EV derived from triple-negative BCC to promote the functions of noncancer cells, such as tissue stem cells, in tumorigenesis.
- Subjects
TRIPLE-negative breast cancer; CANCER stem cells; EXTRACELLULAR vesicles; CANCER cells; CANCER invasiveness; EXTRACELLULAR matrix proteins
- Publication
Frontiers in Oncology, 2024, p1
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2024.1346312