title: Biological characterization and analysis of metastasis-related genes in cell lines derived from the primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva.
abstract: Controlling metastatic lesions is an important part of improving cancer prognosis, in addition to controlling the primary lesion. There have been numerous histological studies on primary and metastatic lesions, but little basic research has been performed using cell lines from primary and metastatic lesions belonging to the same patient. In this study, we successfully established a cell line derived from lower gingival carcinoma (WK2) as well as a line derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. We then investigated the biological characteristics of the cancer cell lines from these primary and metastatic lesions and analyzed metastasis-related genes. Comparison of the biological characteristics in vitro showed that WK3F had higher cell proliferation ability and shorter cell doubling time than WK2. WK3F also had increased cell migratory ability and higher invasive and self-replication abilities. Heterotransplantation into nude mice resulted in high tumor formation rates in the tongue and high metastasis rates in the cervical lymph nodes. Changes in WK2 and WK3F gene expression were then comprehensively analyzed using microarrays. Genes with increased expression in WK3F compared to WK2 were extracted when the Z-score was ≥2.0 and the ratio was ≥5.0, while genes with reduced expression in WK3F compared to WK2 were extracted when the Z-score was ≤-2.0 and the ratio was ≤0.2; differences were found in 604 genes. From these, MAGEC1 (88.0-fold), MMP-7 (18.6-fold), SNAI1 (6.6-fold), MACC1 (6.2-fold), and HTRA1 (0.012-fold) were selected as metastasis-related candidate genes. The results suggest that these molecules could be important for clarifying the mechanisms that regulate metastasis and provide new therapeutic targets for inhibiting tumor invasion.
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujinaga
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kumamaru
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ohyama
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ikari
authors.affiliation: Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Mitsuho
authors.initials: M
authors.lastname: Onimaru
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Naonari
authors.initials: N
authors.lastname: Akimoto
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Jogo
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005887:Gingival Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009374:Neoplasms, Experimental; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*
chemical_list: D009363:Neoplasm Proteins