Saha Aritra, Anirvan Prajna
Department of Internal Medicine, Assam Medical College and Hospital, Dibrugarh 786002, Assam, India.
https://orcid.org/0000-0003-4705-7453.
Ecancermedicalscience. 2020 Sep 9;14:1099. doi: 10.3332/ecancer.2020.1099. eCollection 2020.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has affected millions worldwide and has been found to cause severe disease in patients with underlying comorbidities. In patients with known malignancies, in addition to constraints in routine healthcare, the risk of being susceptible to developing severe forms of the disease is of grave concern. While follow-up studies on survivors of the severe acute respiratory syndrome (SARS) 2003 outbreak revealed increased susceptibility to infections, tumours and cardiovascular abnormalities, recent studies implicating angiopoietin 2 in induction of inflammatory intussusceptive angiogenesis and diffuse alveolar damage in COVID-19 patients raises the possibility of progression of carcinogenetic processes in patients with known malignancies. Angiotensin converting enzyme-2 (ACE-2) mediated cellular entry of SARS-Cov2 leads to receptor shedding of ACE-2 and disrupts the renin angiotensin aldosterone axis (RAAS). This augments the pro-inflammatory and proliferative effects of RAAS, while attenuating the anti-inflammatory and anti-proliferative angiotensin 1-7 /Mas pathway. Angiopoietin-2, a molecule responsible for angiogenesis and cancer progression which corelates with tumour load in certain cancers, is upregulated by angiotensin 2-AT1 Receptor axis. Tumour microenvironment-comprising of various cells, blood vessels and extra cellular matrix which express the RAAS peptides-plays a key role in cancer initiation, progression and metastasis. Angiotensin 2 induces the formation of a desmoplastic environment, favouring cancer cell growth. ACE-2 downregulation causes bradykinin accumulation which may exert its proliferative action via mitogen activated protein kinase pathways which has established roles in cancers of breast and kidney. In addition to cytokine storm causing organ damage, acute inflammation in COVID-19 may also cause epithelial mesenchymal transition and heat shock protein 27 phosphorylation, both of which are key mediators in cancer signalling pathways. We hypothesise that SARS-Cov2, by impacting the RAAS and immune system, has the potential to cause tumour cell proliferation, apoptosis evasion and metastasis, thereby increasing the possibility of cancer progression in patients with known malignancies.
持续的2019冠状病毒病（COVID-19）大流行已影响全球数百万人，并已发现会在患有基础合并症的患者中引发严重疾病。在已知患有恶性肿瘤的患者中，除了常规医疗保健受到限制外，易发展为该疾病严重形式的风险也备受关注。虽然对2003年严重急性呼吸综合征（SARS）疫情幸存者的随访研究显示其对感染、肿瘤和心血管异常的易感性增加，但最近有关血管生成素2在COVID-19患者炎症性套叠式血管生成和弥漫性肺泡损伤诱导中的作用的研究，增加了已知恶性肿瘤患者致癌过程进展的可能性。血管紧张素转换酶2（ACE-2）介导SARS-CoV2的细胞进入，导致ACE-2的受体脱落，并破坏肾素血管紧张素醛固酮轴（RAAS）。这增强了RAAS的促炎和增殖作用，同时减弱了抗炎和抗增殖的血管紧张素1-7 / Mas途径。血管生成素-2是一种负责血管生成和癌症进展的分子，在某些癌症中与肿瘤负荷相关，它由血管紧张素2-AT1受体轴上调。肿瘤微环境由表达RAAS肽的各种细胞、血管和细胞外基质组成，在癌症的发生、进展和转移中起关键作用。血管紧张素2诱导促结缔组织增生环境的形成，有利于癌细胞生长。ACE-2下调导致缓激肽积累，缓激肽可能通过丝裂原活化蛋白激酶途径发挥其增殖作用，该途径在乳腺癌和肾癌中已确立作用。除了细胞因子风暴导致器官损伤外，COVID-19中的急性炎症还可能导致上皮间质转化和热休克蛋白27磷酸化，这两者都是癌症信号通路中的关键介质。我们假设，SARS-CoV2通过影响RAAS和免疫系统，有可能导致肿瘤细胞增殖、凋亡逃避和转移，从而增加已知恶性肿瘤患者癌症进展的可能性。
