Department of Surgery, Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, USA.
Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
Int J Mol Sci. 2020 Mar 9;21(5):1872. doi: 10.3390/ijms21051872.
Although molecular mechanisms driving tumor progression have been extensively studied, the biological nature of the various populations of circulating tumor cells (CTCs) within the blood is still not well understood. Tumor cell fusion with immune cells is a longstanding hypothesis that has caught more attention in recent times. Specifically, fusion of tumor cells with macrophages might lead to the development of metastasis by acquiring features such as genetic and epigenetic heterogeneity, chemotherapeutic resistance, and immune tolerance. In addition to the traditional FDA-approved definition of a CTC (CD45-, EpCAM+, cytokeratins 8+, 18+ or 19+, with a DAPI+ nucleus), an additional circulating cell population has been identified as being potential fusions cells, characterized by distinct, large, polymorphonuclear cancer-associated cells with a dual epithelial and macrophage/myeloid phenotype. Artificial fusion of tumor cells with macrophages leads to migratory, invasive, and metastatic phenotypes. Further studies might investigate whether these have a potential impact on the immune response towards the cancer. In this review, the background, evidence, and potential relevance of tumor cell fusions with macrophages is discussed, along with the potential role of intercellular connections in their formation. Such fusion cells could be a key component in cancer metastasis, and therefore, evolve as a diagnostic and therapeutic target in cancer precision medicine.
尽管已经广泛研究了推动肿瘤进展的分子机制，但血液中循环肿瘤细胞（CTC）的各种群体的生物学性质仍未得到很好的理解。肿瘤细胞与免疫细胞融合是一个由来已久的假说，最近引起了更多的关注。具体来说，肿瘤细胞与巨噬细胞融合可能会通过获得遗传和表观遗传异质性、化疗耐药性和免疫耐受性等特征，导致转移的发展。除了传统的 FDA 批准的 CTC（CD45-，EpCAM+，细胞角蛋白 8+、18+或 19+，具有 DAPI+核）定义外，还鉴定出另一种循环细胞群体作为潜在的融合细胞，其特征是具有独特的、大的、多形核的癌相关细胞，具有上皮和巨噬细胞/髓样表型的双重表型。肿瘤细胞与巨噬细胞的人工融合导致迁移、侵袭和转移表型。进一步的研究可能会探讨这些细胞是否对癌症的免疫反应产生潜在影响。在这篇综述中，讨论了肿瘤细胞与巨噬细胞融合的背景、证据和潜在相关性，以及细胞间连接在其形成中的潜在作用。这些融合细胞可能是癌症转移的关键组成部分，因此作为癌症精准医学的诊断和治疗靶点不断发展。
