Tumor-Cell-Macrophage Fusion Cells as Liquid Biomarkers and Tumor Enhancers in Cancer

• Published in: International journal of molecular sciences 2020-03, Vol.21 (5), p.1872
• Main Authors: Manjunath, Yariswamy, Porciani, David, Mitchem, Jonathan B, Suvilesh, Kanve N, Avella, Diego M, Kimchi, Eric T, Staveley-O'Carroll, Kevin F, Burke, Donald H, Li, Guangfu, Kaifi, Jussuf T
• Format: Article
• Language: English
• Subjects: Animals; Biology; Biomarkers; Biomarkers, Tumor - blood; Blood circulation; Bone marrow; Cancer; Cancer therapies; CD45 antigen; Cell fusion; Chemoresistance; circulating tumor cells; Diagnostic systems; Enhancers; Epigenetics; fusion cells; Humans; Immune response; Immune system; Immunological tolerance; Invasiveness; liquid biomarkers; Liver cancer; Macrophages; Macrophages - pathology; Membranes; Metastases; Metastasis; Molecular modelling; Neoplasm Metastasis - pathology; Neoplasms - blood; Neoplasms - pathology; Neoplastic Cells, Circulating - pathology; Nuclei (cytology); Patients; Phenotypes; Physiology; Polyethylene glycol; Precision medicine; Review; Stem cells; Therapeutic applications; Tumor cells; Tumor necrosis factor-TNF; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.