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.

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 triple-negative BCC (MpEV) significantly induced the paracrine effects of adipose tissue-derived 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 triple-negative 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-2 M-protein in altering the cellular communication between cancer cells and other non-cancer cells inside the tumor microenvironment via EV. Specifically, M-proteins induced the ability of EV derived from triple-negative BCC to promote the functions of non-cancer cells, such as tissue stem cells, in tumorigenesis.

SARS-CoV-2 M Protein Facilitates Malignant Transformation of Breast Cancer Cells.

Coronavirus disease 2019 (COVID-19) has spread faster due to the emergence of SARS-CoV-2 variants, which carry an increased risk of infecting patients with comorbidities, such as breast cancer. However, there are still few reports on the effects of SARS-CoV-2 infection on the progression of breast cancer, as well as the factors and mechanisms involved. In the present study, we investigated the impact of SARS-CoV-2 proteins on breast cancer cells (BCC). The results suggested that SARS-CoV-2 M protein induced the mobility, proliferation, stemness and in vivo metastasis of a triple-negative breast cancer (TNBC) cell line, MDA-MB-231, which are involved in the upregulation of NFκB and STAT3 pathways. In addition, compared to MDA-MB-231 cells, the hormone-dependent breast cancer cell line MCF-7 showed a less response to M protein, with the protein showing no effects of promoting proliferation, stemness, and in vivo metastasis. Of note, coculture with M protein-treated MDA-MB-231 cells significantly induced the migration, proliferation, and stemness of MCF-7 cells, which are involved in the upregulation of genes related to EMT and inflammatory cytokines. Therefore, SARS-CoV-2 infection might promote the ability of aggressive BCC to induce the malignant phenotypes of the other non-aggressive BCC. Taken together, these findings suggested an increased risk of poor outcomes in TNBC patients with a history of SARS-CoV-2 infection, which required a long-term follow-up. In addition, the inhibition of NFκB and STAT3 signaling pathways is considered as a promising candidate for the treatment of worsen clinical outcomes in TNBC patients with COVID-19.

Human papillomavirus infection among women in South and North Vietnam.

The incidence rate of invasive cervical carcinoma (ICC) is 4-fold higher in Ho Chi Minh City, in the South of Vietnam, than in Hanoi, in the North. Thus, we explored the prevalence of and the risk factors for human papillomavirus (HPV) infection in these 2 areas. A population-based random sample of married women aged 15-69 years were interviewed and had a gynaecological examination in the urban district of Ho Chi Minh City and in a peri-urban district in Hanoi. HPV DNA detection was performed using a GP5+/6+ primer-mediated PCR enzyme immunoassay. A total of 922 women from Ho Chi Minh and 994 from Hanoi, for whom a Pap smear and HPV-status were available, were evaluated. HPV DNA was detected among 10.9% of women in Ho Chi Minh City and 2.0% in Hanoi (age standardized prevalence, world standard population: 10.6% and 2.3%, respectively). In the 2 areas combined, 30 different HPV types were found, the most common being HPV 16 (in 14 single and 18 multiple infections), followed by HPV 58, 18 and 56. A peak of HPV DNA detection in women younger than age 25 was found in Ho Chi Minh City (22.3%) but not in Hanoi. Major risk factors for HPV DNA detection were indicators of sexual habits, most notably the presence of HSV-2 antibodies, nulliparity and the current use of oral contraceptives. Women in Hanoi showed the lowest HPV prevalence ever reported so far, suggesting that HPV has not spread widely in this population. As expected, HPV prevalence in a population seemed to be closely correlated with ICC incidence rates.