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Fusion between cancer cells and macrophages occurs in a murine model of spontaneous neu+ breast cancer without increasing its metastatic potential
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Michela Lizier1,2,3, Achille Anselmo2, Stefano Mantero1,2, Francesca Ficara1,2, Marianna Paulis1,2, Paolo Vezzoni1,2, Franco Lucchini3 and Giovanni Pacchiana1,2
1 Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan,Italy
2 Humanitas Clinical and Research Center, Rozzano, Milan, Italy
3 Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Milan, Italy
Franco Lucchini, email:
Keywords: neu oncogene; cell fusion; metastatic spread; macrophage; reporter genes
Received: April 20, 2016 Accepted: August 11, 2016 Published: August 22, 2016
Cell fusion between neoplastic and normal cells has been suggested to play a role in the acquisition of a malignant phenotype. Several studies have pointed to the macrophage as the normal partner in this fusion, suggesting that the fused cells could acquire new invasive properties and become able to disseminate to distant organs. However, this conclusion is mainly based on studies with transplantable cell lines. We tested the occurrence of cell fusion in the MMTV-neu model of mouse mammary carcinoma. In the first approach, we generated aggregation chimeras between GFP/neu and RFP/neu embryos. Tumor cells would display both fluorescent proteins only if cell fusion with normal cells occurred. In addition, if cell fusion conferred a growth/dissemination advantage, cells with both markers should be detectable in lung metastases at increased frequency. We confirmed that fused cells are present at low but consistent levels in primary neoplasms and that the macrophage is the normal partner in the fusion events. Similar results were obtained using a second approach in which bone marrow from mice carrying the Cre transgene was transplanted into MMTV-neu/LoxP-tdTomato transgenic animals, in which the Tomato gene is activated only in the presence of CRE recombinase. However, no fused cells were detected in lung metastases in either model. We conclude that fusion between macrophages and tumor cells does not confer a selective advantage in our spontaneous model of breast cancer, although these data do not rule out a possible role in models in which an inflammation environment is prominent.
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