Involvement of decreased expression of KAI1 in carcinogenesis and lymph node metastasis of lower gingival squamous cell carcinomas

Abstract

KAI1 is a tumor suppressor gene originally identified in prostate cancer. Recent studies of oral cancer, including our investigations, have shown frequent down-regulation of KAI1 expression in many tumor types, whereas mutation of the gene is infrequent. However, the role of the down-expression of KAI1 in oncogenesis and the progression of oral carcinoma remains unclear. In this study, we analyzed the mutational status of KAI1 and both the mRNA and protein levels of the gene in a series of gingival carcinomas and precancerous lesions (20 leukoplakias, 50 squamous cell carcinomas, and 20 lymph node metastatic tumors) . Although no mutation was found in any sample tested, immunohistochemical studies revealed high frequencies of KAI1 down-regulation not only in the metastatic tumors (20 of 20, 100 %) , but also in the primary carcinomas (39 of 50, 78 %) and leukoplakias (9 of 20, 45 %). Down-regulation of KAI1 protein expression was significantly related to carcinogenesis and metastasis (precancerous lesions, primary carcinomas, and metastatic tumors) (p<0.001) as well as to lymph node metastasis (p=0.0022). RT PCR analysis confirmed these results. Therefore, suppressed expression of KAI1 was suggested to play clinically significant roles in carcinogenesis and lymph node metastasis .

Roles of KAI1 and nm23 in lymphangiogenesis and lymph metastasis of laryngeal squamous cell carcinoma

“…KAI1 regulates cell movement, metastasis, and proliferation by regulating cell adhesion [ 6 ]. The low expression of KAI1 induces malignant transformation and tumor progression, leading to lymphatic metastasis and poor survival [ 7 – 9 ]. Downregulation of KAI1 expression is closely related with carcinogenesis and metastasis of lower gingival SCC [ 7 ], whereas KAI1 overexpression inhibits lymphangiogenesis and lymph node metastasis of pancreatic tumors [ 10 ].…”

“…The low expression of KAI1 induces malignant transformation and tumor progression, leading to lymphatic metastasis and poor survival [ 7 – 9 ]. Downregulation of KAI1 expression is closely related with carcinogenesis and metastasis of lower gingival SCC [ 7 ], whereas KAI1 overexpression inhibits lymphangiogenesis and lymph node metastasis of pancreatic tumors [ 10 ]. Given the important role of KAI1 in tumorgenesis, development, invasion, and metastasis, KAI1 may be used as a molecular marker for determining invasiveness, metastasis, and prognosis of LSCC [ 11 , 12 ].…”