Nguyen Hoai-Nga Thi, Kawahara Marie, Vuong Cat-Khanh, Fukushige Mizuho, Yamashita Toshiharu, Ohneda Osamu
Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan.
Front Oncol. 2022 Jun 7;12:923467. doi: 10.3389/fonc.2022.923467. eCollection 2022.
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 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 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.
2019冠状病毒病（COVID-19）因严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现而传播得更快，这些变体增加了感染合并症患者（如乳腺癌患者）的风险。然而，关于SARS-CoV-2感染对乳腺癌进展的影响以及相关因素和机制的报道仍然很少。在本研究中，我们调查了SARS-CoV-2蛋白对乳腺癌细胞（BCC）的影响。结果表明，SARS-CoV-2 M蛋白诱导了三阴性乳腺癌（TNBC）细胞系MDA-MB-231的迁移、增殖、干性和转移，这与NFκB和STAT3信号通路的上调有关。此外，与MDA-MB-231细胞相比，激素依赖性乳腺癌细胞系MCF-7对M蛋白的反应较小，该蛋白对促进增殖、干性和转移没有作用。值得注意的是，与经M蛋白处理的MDA-MB-231细胞共培养显著诱导了MCF-7细胞的迁移、增殖和干性，这与上皮-间质转化（EMT）相关基因和炎性细胞因子的上调有关。因此，SARS-CoV-2感染可能会促进侵袭性BCC诱导其他非侵袭性BCC恶性表型的能力。综上所述，这些发现表明，有SARS-CoV-2感染史的TNBC患者预后不良的风险增加，这需要长期随访。此外，抑制NFκB和STAT3信号通路被认为是治疗COVID-19的TNBC患者临床结局恶化的一个有前景的候选方法。
