Biomarkers Identification of Nasopharyngeal Carcinoma through Analyzing Cancer Stem Cells
| Autor: | Jung-Chi Chao, 趙容琪 |
|---|---|
| Rok vydání: | 2011 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 99 Nasopharyngeal carcinoma (NPC) is common in certain regions of Southeast China and Africa. NPC arises from the mucosal epithelium of the nasopharynx, where it is difficult to be diagnosed. Although the prognosis of individuals with NPC has greatly improved in the past decades (up to 100 % at early stage), and with a low recurrence rate (5 %~10 %), the survival of recurrence is rather low (up to 30 %), and is usually accompanied by metastasis and therapeutic resistance. Despite the useful NPC marker EBV VCA-IgA, other cellular biomarkers are still important for diagnosis and prognosis. In this study, we intend to identify biomarkers for NPC via cancer stem cells. We used two NPC cell lines established from Taiwanese patients, Tw01 cells (WHO type I, keratinizing squamous cell carcinoma) and Tw06 cells (WHO type IIb, undifferentiated carcinoma). Our laboratory has previously established cancer stem cell lines on the basis of three cancer stem cell properties, namely drug resistance, radioresistance and tumor sphere formation. The triple method-selected cells showed notable drug resistance, radioresistance, the ability to sustain anoikis (suspension induced apoptosis) and most importantly, tumorigenicity in mice. Here we found out that cancer stem cells maintained in suspension culture (growth factor supplemented media) showed increasing stemness and EMT markers as time goes on. The cells also gradually became quiescent, while rapid proliferation could be induced after they were transferred to serum supplemented media in an attachable environment. By comparing microarray data between parental and cancer stem cells, there were 76 and 202 upregulated secretory proteins in Tw01 and Tw06 cancer stem cells, respectively. We focused on 36 genes that are in common. According to their functions, the top 10 most cancer-related targets were chosen to confirm their mRNA expression by quantitative PCR. Two candidates, fibronectin 1 (FN1) and interleukin-1A (IL-1A) were significantly up-regulated in cancer stem cell cultures, but not in their parental cells. The two genes were also highly expressed at protein levels either in cell lysates or culture media, as assayed by ELISA. However, so far as we followed, only a few mice grown tumor at their injection site, and there were no positive correlations of fibronectin 1 (FN1) and interleukin-1 alpha (IL-1 alpha) expression with tumor progression in animal studies. In conclusion, in vitro. studies indicated FN1 and IL-1 alpha were potential candidates for NPC biomarker, but further in vivo. studies will be proceeded to confirm our findings. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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