Background To investigate the differential expression levels of thymosin β10 (Tβ10) and the corresponding changes of actin filament organization in human tumor cell lines with different metastatic potential.Methods ...Background To investigate the differential expression levels of thymosin β10 (Tβ10) and the corresponding changes of actin filament organization in human tumor cell lines with different metastatic potential.Methods Four groups of nine human tumor cell lines with different metastatic potential were analyzed for the amount of Tβ10 mRNAs by Northern blot and for their peptide expression levels by immunohistochemistry. The filamentous actin (F-actin) was observed by staining of TRITC-phalloidin to detect changes in actin organization.Results In comparison with non-/weakly metastatic counterparts, Tβ10 was upregulated in highly metastatic human lung cancer, malignant melanoma and breast cancer cell lines. Staining of TRITC-phalloidin revealed less actin bundles, a fuzzy network of shorter filaments and some F-actin aggregates in the highly metastatic tumor cells. Meanwhile, the actin filaments were robust and orderly arranged in the non-/weakly metastatic cancer cell lines.Conclusion Tβ10 levels correlate positively with the metastatic capacity in human tumors currently examined. The increasing metastatic potential of tumor cells is accompanied by a loss of F-actin, poorly arranged actin skeleton organizations and presence of F-actin aggregates. There is a consistent correlation between the elevated Tβ10 expression and the disrupted actin skeleton.展开更多
文摘目的:胸腺肽β10(thymosinβ10,TMSβ10)在部分恶性肿瘤中呈过表达状态,但其在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达尚无报道。本研究旨在探讨TMSβ10在OSCC组织中的表达和潜在的作用机制。方法:收集OSCC样本基因芯片和RNA测序表达矩阵,提取TMSβ10 mRNA表达值;采用标准化均值差(standardized mean difference,SMD)总受试者工作特征(summary receiver operating characteristic,SROC)曲线评估TMSβ10表达的临床价值,并进行TMSβ10相关基因的功能富集分析,再以免疫组织化学实验进行验证。结果:与252份非癌口腔组织相比,TMSβ10在677例OSCC组织中显著升高[SMD=1.68(0.95~2.42)],且对于OSCC具有高区分能力[SROC曲线下面积(area under the curve,AUC)=0.95,95%CI为0.92~0.96]。TMSβ10相关基因生物学功能主要富集于伤口愈合、蛋白酶体蛋白等方面。此外,多个数据集的分析显示纤维连接蛋白1(fibronectin 1,FN1)与TMSβ10基因之间存在显著的正相关性(r为0.34~0.83,均P<0.05),被鉴定为TMSβ10伤口愈合通路中的枢纽基因。结论:TMSβ10表达上调可能具有促进OSCC发生的作用。
基金This work was supported by the National Science Foundation of China ( No. 30170363 ) Key Project on Science and Technology of Chinese Ministry of Education ( No. 01003 ) the Major State Basic Research Development Program of China (No. 2002CB513105 )
文摘Background To investigate the differential expression levels of thymosin β10 (Tβ10) and the corresponding changes of actin filament organization in human tumor cell lines with different metastatic potential.Methods Four groups of nine human tumor cell lines with different metastatic potential were analyzed for the amount of Tβ10 mRNAs by Northern blot and for their peptide expression levels by immunohistochemistry. The filamentous actin (F-actin) was observed by staining of TRITC-phalloidin to detect changes in actin organization.Results In comparison with non-/weakly metastatic counterparts, Tβ10 was upregulated in highly metastatic human lung cancer, malignant melanoma and breast cancer cell lines. Staining of TRITC-phalloidin revealed less actin bundles, a fuzzy network of shorter filaments and some F-actin aggregates in the highly metastatic tumor cells. Meanwhile, the actin filaments were robust and orderly arranged in the non-/weakly metastatic cancer cell lines.Conclusion Tβ10 levels correlate positively with the metastatic capacity in human tumors currently examined. The increasing metastatic potential of tumor cells is accompanied by a loss of F-actin, poorly arranged actin skeleton organizations and presence of F-actin aggregates. There is a consistent correlation between the elevated Tβ10 expression and the disrupted actin skeleton.
