Pawelek JM, Chakraborty AK.. Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis. Nat Rev Cancer 8: 377-386

Department of Dermatology and the Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-08059, USA.
Nature Reviews Cancer (Impact Factor: 37.4). 06/2008; 8(5):377-86. DOI: 10.1038/nrc2371
Source: PubMed


The causes of metastasis remain elusive despite vast information on cancer cells. We posit that cancer cell fusion with macrophages or other migratory bone marrow-derived cells (BMDCs) provides an explanation. BMDC-tumour hybrids have been detected in numerous animal models and recently in human cancer. Molecular studies indicate that gene expression in such hybrids reflects a metastatic phenotype. Should BMDC-tumour fusion be found to underlie invasion and metastasis in human cancer, new approaches for therapy would surely follow.

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Available from: Ashok K Chakraborty, Mar 22, 2014
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    • "Sixty years later, this idea was expanded by proposing that hybridization of tumor cells with lymphocytes results in metastatic cells [37] and that cell fusion promotes the phenotypic and genotypic diversity of tumors [38]. The best defended theory is cancer cell fusion with macrophages or other migratory bone marrow-derived cells which provides a unifying explanation for metastasis [39]. Although host cell-cancer cell fusion has been demonstrated and well documented in animals [40], there is as yet far less information on human cancer. "
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    ABSTRACT: Background: Recently antiangiogenic therapy with bevacizumab has shown a high but transient efficacy in glioblastoma (GBM). Indeed, GBM is one of the most angiogenic human tumors and endothelial proliferation is a hallmark of the disease. We therefore hypothesized that tumor cells may participate in endothelial proliferation of GBM. Materials and methods: We used EGFR FISH Probe to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to identify endothelial cells. Endothelial and GBM cells were grown separately, labeled with GFP and DsRed lentiviruses, and then cocultured with or without contact. Results: In a subset of GBM tissues, we found that several tumor endothelial cells carry EGFR amplification, characteristic of GBM tumor cells. This observation was reproduced in vitro: when tumor stem cells derived from GBM were grown in the presence of human endothelial cells, a fraction of them acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF). By transduction with GFP and DsRed expressing lentiviral vectors, we demonstrate that this phenomenon is due to cell fusion and not transdifferentiation. Conclusion: A fraction of GBM stem cells thus has the capacity to fuse with endothelial cells and the resulting hybrids may participate in tumor microvascular proliferation and in treatment resistance.
    BioMed Research International 04/2014; 2014:827327. DOI:10.1155/2014/827327 · 2.71 Impact Factor
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    • "At least some of these hybrids become metastatic, exhibiting both motility and continuous cell division. The model is simple— white blood cell + non-metastatic cancer cell = metastatic cancer cell—yet it provides a profound and unifying explanation for metastasis (Figure 1)[4]. Highlights of Aichel's hypothesis and ensuing supportive evidence are presented in Table 1. "
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    ABSTRACT: This perspective article highlights the leukocyte-cancer cell hybrid theory as a mechanism for cancer metastasis. Beginning from the first proposal of the theory more than a century ago and continuing today with the first proof for this theory in a human cancer, the hybrid theory offers a unifying explanation for metastasis. In this scenario, leukocyte fusion with a cancer cell is a secondary disease superimposed upon the early tumor, giving birth to a new, malignant cell with a leukocyte-cancer cell hybrid epigenome.
    Ai zheng = Aizheng = Chinese journal of cancer 03/2014; 33(3):133-9. DOI:10.5732/cjc.013.10243 · 2.16 Impact Factor
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    • "Moreover, the elevated soluble serum ICMA-1 and VCAM-1 in patients have also been shown to be associated with the inflammatory reactions within tissues [27-31]. Recently novel metastatic theory has indicated that the cancer cell-leukocyte fusion play potential role in the cancer metastasis [33]. Therefore, the issue about whether resistin-induced HCC adhesion to the endothelium through ICAM-and VCAM-1 in HCC is regulated by leukocytes warrants further exploration. "
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    ABSTRACT: Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects. Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs. These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis.
    BMC Cancer 02/2014; 14(1):112. DOI:10.1186/1471-2407-14-112 · 3.36 Impact Factor
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