KITENIN represents a more aggressive phenotype in a murine model of oral cavity squamous carcinoma.

OBJECTIVE: To investigate the tumor invasiveness and early lung metastasis associated with KITENIN in a murine model of oral cavity squamous carcinoma. STUDY DESIGN: Cross-sectional study with planned data collection. SETTING: Department of Otolaryngology-Head and Neck Surgery, Medical Research Center for Gene Regulation, and Pathology, Chonnam National University Medical School and Hwasun Hospital. SUBJECTS AND METHODS: The cDNA of KITENIN and vector only were transfected into the SCC VII (murine squamous cell line) cells. The suspension of 5 x 10(5)/mL viable KITENIN- or vector-transfected SCC VII cells was injected into the floor of the mouth of C3H/HeJ syngeneic mice, deep into the mylohyoid muscle via the intraoral approach. From the first to the sixth week after injection, tumor, lung, liver, and brain tissues were obtained. RESULTS: For all groups, the tumor invaded the superficial musculature of the floor of the mouth, the deep musculature of the floor of the mouth, the salivary glands, perineural tissue, bone, and skin, sequentially. Lung metastases developed multiple focal nodular patterns at first and then became more extensive. Earlier and more aggressive tumor invasion into the deep floor of the mouth musculature, salivary glands, perineural tissue, bone, and skin was observed in the KITENIN-transfected group compared to the vector-only group. An earlier and more extensive lung metastasis was observed in the KITENIN group. CONCLUSION: An antisense KITENIN strategy might inhibit distant metastasis and the progression of head and neck squamous cell carcinoma.

KITENIN increases invasion and migration of mouse squamous cancer cells and promotes pulmonary metastasis in a mouse squamous tumor model.

KAI1 C-terminal interacting tetraspanin (KITENIN) is reported to promote metastasis in mouse colon cancer models. We investigated the role of KITENIN on the progression of squamous cell carcinoma (SCC). In a preliminary clinical study using resected tissues from head and neck SCC patients, KITENIN was highly expressed in tumors and metastatic lymph nodes, while KAI1 was more increased in adjacent mucosa than in tumor. KITENIN-transfected mouse squamous cancer (SCC VII/KITENIN) cells showed significantly higher invasion, migration, and proliferation than empty vector-transfected cells. In syngeneic mouse squamous tumor models, more increased tumor volume and enhanced lung metastasis were found in SCC VII/KITENIN cells-injected mice. Thus, KITENIN increases invasion and migration of squamous cancer cells and thereby promotes distant metastasis in mouse squamous tumor models.