title: Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential.
abstract: Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression.
authors.affiliation: Department of Oral & Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Shandong Province, China; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Song
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China; Department of Stomatology, Liu Zhou People׳s Hospital, Guangxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Ting-Lin
authors.initials: TL
authors.lastname: Yan
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, China; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China. Electronic address: liuke.1999@aliyun.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, China; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China. Electronic address: shangzhengjun@hotmail.com.
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Shang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002450:Cell Communication; D002459:Cell Fusion; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005455:Fluorescent Antibody Technique; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017404:In Situ Hybridization, Fluorescence; D053538:Keratin-18 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009681:Nuclear Fusion; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C488421:KRT18 protein, human; D053538:Keratin-18; D014746:Vimentin; D002945:Cisplatin
keywords: Cell fusion; Chemoresistance; Endothelial cell; Nuclear fusion; Oral cancer; RFP; eGFP