KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma

Down-regulation of KAI1 expression has been shown to be associated with for mation of metastases or disease progression in prostate and pancreatic canc er. In the present study we analyzed the expression pattern of KAI1 in meta static and nonmetastatic hepatocellular carcinomas (HCCs) in comparison wit h normal livers to evaluate whether alteration of KAI1 also facilitates the metastatic ability in this malignancy. Thirty-nine primary HCCs and 10 nor mal liver tissue samples were studied for KAI1 messenger RNA (mRNA) express ion with use of Northern blot analysis and in situ hybridization. By Northe rn blot analysis, moderate to strong KAI1 mRNA expression was present in no rmal liver samples. In contrast, KAI1 mRNA expression in tissue samples of primary HCCs was markedly decreased compared with normal controls. The norm al/ tumor ratio of KAI1 mRNA expression was 2.6:1 (P < .01). Primary HCCs t hat gave rise to metastasis showed significantly lower KAI1 mRNA levels tha n nonmetastasized HCCs (P < .05). As seen by in situ hybridization, moderat e to strong cytoplasmic KAI1 mRNA staining was present in almost all normal hepatocytes. Bile ducts, blood vessels, and connective tissue showed no or only faint KAI1 mRNA expression in the normal liver samples. In nonmetasta tic HCCs, the cancer cells exhibited in situ hybridization signals that wer e similar to the normal controls. In contrast, most of the primary HCC cell s in samples with metastases showed only faint or moderate KAI1 mRNA expres sion predominantly in the perinuclear regions. When KAI1 mRNA expression of primary hepatocellular cancer cells was compared with metastasized cancer cells in lymph nodes, with intrahepatic satellite metastasis, or with perit oneal metastasis in the same patients, significantly lower (P < .01) KAI1 m RNA. levels were present in the metastasized HCC cells. Reduced KAI1 mRNA i n HCC cells seems to influence their metastatic ability and thereby enhance s the malignant potential of HCC.