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

Takahiro Fujinaga, Kumamaru Wataru, Tsuyoshi Sugiura, Yosuke Kobayashi, Yukiko Ohyama, Tatsuya Ikari, Mitsuho Onimaru, Naonari Akimoto, Rumi Jogo, Yoshihide Mori

Research output: Contribution to journalArticle

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 micro-arrays. 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.

Original languageEnglish
Pages (from-to)1614-1624
Number of pages11
JournalInternational journal of oncology
Volume44
Issue number5
DOIs
Publication statusPublished - Jan 1 2014

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Gingiva
Squamous Cell Carcinoma
Lymph Nodes
Neoplasm Metastasis
Cell Line
Genes
Neoplasms
Matrix Metalloproteinases
Tongue
Nude Mice
Cell Proliferation
Carcinoma
Gene Expression
Research

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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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. / Fujinaga, Takahiro; Wataru, Kumamaru; Sugiura, Tsuyoshi; Kobayashi, Yosuke; Ohyama, Yukiko; Ikari, Tatsuya; Onimaru, Mitsuho; Akimoto, Naonari; Jogo, Rumi; Mori, Yoshihide.

In: International journal of oncology, Vol. 44, No. 5, 01.01.2014, p. 1614-1624.

Research output: Contribution to journalArticle

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