Schramm Henning M
Institute for Integral Cancer Research (IFIK), CH-4144 Arlesheim/Switzerland.
J Cancer. 2019 Jun 9;10(16):3798-3809. doi: 10.7150/jca.31364. eCollection 2019.
Cancer cells express multiple markers expressed by mesenchymal as well as myeloid cells in common and in addition specific markers of the myeloid lineages, especially those of dendritic cells, macrophages and preosteoclasts. It has also been possible to identify monocyte-macrophage gene clusters in cancer cell specimens as well as in cancer cell lines. Accordingly, like myeloid cells cancer cells often express pro-inflammatory cytokines, and consequently the carcinoma may be perceived by the organism as a primary inflammatory process comparable to the immune inflammatory reactions in the eye or in the case of arthritis. This would explain why a carcinoma may induce a certain alarm state in the organism by increasing a fatal sympathetic tone in the patient, supplying the carcinomas with nutrients at the cost of other requirements, inducing tolerance against the cancer cells mistaken as myeloid cells, provoking fibrosis and neoangiogenesis, and increasing inflammatory cells at the carcinoma site. This seemingly inflammatory process of Epithelial-Myeloid-Transition (EMyeT) is superimposed by the progression of part of the myeloid cancer cells to stages comparable to preosteoclasts and osteoclasts, and their development to metastasizing carcinomas often at the site of bone. This concept of carcinogenesis and malignant progression described here challenges the widely accepted EMT-hypotheses and could deliver the rationale for the various peculiar aspects of cancer and the variety of therapeutic antitumoral measures.
癌细胞表达多种间充质细胞和髓样细胞共有的标志物,此外还表达髓系谱系的特异性标志物,尤其是树突状细胞、巨噬细胞和破骨细胞前体细胞的标志物。在癌细胞标本以及癌细胞系中也能够鉴定出单核细胞 - 巨噬细胞基因簇。因此,与髓样细胞一样,癌细胞通常表达促炎细胞因子,因此机体可能将癌视为一种原发性炎症过程,类似于眼睛或关节炎中的免疫炎症反应。这就解释了为什么癌可能通过增加患者致命的交感神经张力,以牺牲其他需求为代价为癌提供营养,诱导对被误认为是髓样细胞的癌细胞产生耐受性,引发纤维化和新血管生成,并增加癌部位的炎症细胞,从而在机体内诱发某种警报状态。上皮 - 髓样转变(EMyeT)这种看似炎症的过程,还叠加了部分髓样癌细胞发展到类似于破骨细胞前体细胞和破骨细胞的阶段,并常常在骨部位发展为转移性癌。这里描述的这种致癌作用和恶性进展的概念挑战了广泛接受的上皮 - 间质转化(EMT)假说,并可能为癌症的各种特殊方面以及多种治疗性抗肿瘤措施提供理论依据。