| Summary: | 碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 105 === Purpose:
Oral squamous cell carcinoma (OSCC) is the fifth common cancer worldwide. Distant metastasis is rare, but presents extremely poor prognosis clinically. Leukemia inhibitory factor (LIF) has been demonstrated an oncogene in several cancers, and we hypothesis that LIF might play crucial role in OSCC progression and metastasis.
Methods:
LIF expression was detected in OSCC samples by Immunohistochemistry. The ectopic LIF expression and silencing LIF were performed by LIF expression plasmids and short-hairpin RNA transfection in vitro, respectively. Boyden chamber assay was used to check migration and invasion abilities. Proliferation ability was analyzed by MTT. High throughput microarray analysis and GSEA analysis were also included. Statistical analyses were performed with unpaired Student’s two-tailed t test. A P value of <0.05 was considered significant.
Results:
Investigations on clinical parameters of OSCC patient and the expression of LIF revealed that patients with positive lymph node metastasis showed high expression of LIF protein (p = 0.022). Also, patient suffered from advanced cancer stage show high expression of LIF (p =0.002). In vitro, transient and stable knockdown LIF significantly decreased migration and invasion abilities. Moreover, overexpressed LIF could enhance OSCC cell motility (P < 0.05), but showed no effects on proliferation ability. In addition, using high throughput mRNA analysis and GSEA analysis, we identified INHBA as a crucial downstream effecter of LIF-promoted OSCC progression. Transfected with INHBA expression plasmid could significantly restore the migration and invasion abilities in shLIF stable transfectants (P < 0.05).
Conclusion:
Leukemia inhibitory factor contributes to cancer progression by enhancing regional lymphatic spread therefore leads to advanced cancer stage clinically. Regulation of the LIF downstream molecule such as INHBA thus can prohibition the invasion or migration ability of cancer cell, targeting on the leukemia inhibitory factor can be a potential strategy in preventing cancer progression and spreading in future.
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