title: Fusion between cancer cells and macrophages occurs in a murine model of spontaneous neu+ breast cancer without increasing its metastatic potential.
abstract: 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.
authors: Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan,Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.|Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Milan, Italy.
authors: Michela
authors: M
authors: Lizier
authors: Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Achille
authors: A
authors: Anselmo
authors: Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan,Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Stefano
authors: S
authors: Mantero
authors: Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan,Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Francesca
authors: F
authors: Ficara
authors: Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan,Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Marianna
authors: M
authors: Paulis
authors: Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan,Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Paolo
authors: P
authors: Vezzoni
authors: Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Milan, Italy.
authors: Franco
authors: F
authors: Lucchini
authors: Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan,Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Giovanni
authors: G
authors: Pacchiana
mesh_terms: D000818:Animals; D017209:Apoptosis; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation; D019426:Integrases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D009362:Neoplasm Metastasis; D010587:Phagocytosis; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D019076:Transgenes
chemical_list: D049452:Green Fluorescent Proteins; D019426:Integrases; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse; C045073:Cre recombinase
keywords: cell fusion; macrophage; metastatic spread; neu oncogene; reporter genes