title: CD44+ cancer cell-induced metastasis: A feasible neck metastasis model.
abstract: Neck metastasis of oral squamous cell carcinoma (OSCC) indicates a poor prognosis. Few neck metastasis models are currently available for drug trials and clinical research on OSCC. This study constructed a feasible animal model of neck metastasis by using CD44+ stem cell-like cancer cells. Real-time PCR was used to determine the expression levels of several reported cancer stem cell (CSC) markers, including CD44, CD133, ALDH1 and OCT4, in three OSCC cell lines. Magnetic sorting and DiO/DiD labelling were used to isolate subpopulations of cells and monitor cancer cell migration. Sorted and labelled CSC-like cells were injected into the tongue of nude mice. Tumour and metastatic lymph nodes were histologically examined through immunostaining and tracer staining. High rate of metastasis was observed in neck lymph nodes in CD44+ group. This phenomenon was confirmed in clinical OSCC patients, and CD44 expression levels were higher in tumours with lymph node metastasis than in carcinomas in situ. Therefore, we have successfully constructed a neck metastasis model by using CD44+ CSCs. This model can form tumour and show metastases within a short period of time compared with other models; additionally, this model may be used in short-term pharmacological experiments involving animals and in basic clinical studies.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Tian-Fu
authors.initials: TF
authors.lastname: Wu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bu
authors.affiliation: Department of Stomatology of Ruikang Hospital, Guangxi University of Chinese Medicine, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: zhangwf59@whu.edu.cn.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: junjia01@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D050814:Octamer Transcription Factor-3; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase
keywords: Animal model; CD44; Cancer stem cell; Neck metastasis; Oral squamous cell carcinoma; Xenograft