| Summary: | 碩士 === 國立中山大學 === 生物醫學研究所 === 102 === Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. However, current therapeutic modalities for HCC, including surgery, transendothelial embolization (TAE) and radiofrequency ablation (RFA), remain largely ineffectively. One major mechanism underlying the failure for cancer therapy is the presence of cancer stem cells (CSCs), which possess the capability of drug efflux and self renewal. The emergence of CSCs results in resistance and metastasis, which ultimately leads to tumor recurrence. Wnt/β-catenin signaling pathway participates in CSCs genesis and targeting Wnt/β-catenin may hold promise for CSCs control. Leukocyte cell-derived chemotaxin 2 (LECT2) was first isolated as a 16-kDa secreted protein from cultured media of phytohemagglutinin-activated human T-cell leukemia SKW-3 cells. Recent studies suggest that LECT2 may act as a tumor suppressor gene in liver through antagonizing Wnt signaling pathway. However, the detailed mechanism of LECT2 in liver cancer remains unclear. In this study, we first observed that intra-tumor LECT2 gene delivery effectively suppressed the progression of orthotopic Novikoff hepatoma in rats through apoptosis induction, angiogenesis blockade and cancer stemness inhibition. Subsequently, we investigated the role of LECT2 on oncogenic behaviors and stemness of hepatoma cells. Despite of marginal effect on proliferation, recombinant LECT2 dose-dependently inhibited the migration, invasion and anchorage-independent growth of HCC cells. Besides, LECT2 application attenuated the epithelial-mesenchymal transition (EMT), drug-efflux and self-renewal capabilities of HCC cells. This was correlated with the downregulation of EMT marker genes, Wnt/β-catenin signaling pathway and c-Met activation. In summary, LECT2 suppresses HCC progression via attenuating the hepatic cancer stemness.
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