惡性神經膠質瘤是一種致死率高的癌症。研究指出，癌細胞高度轉移侵襲特性是腦癌病患的死亡主因。目前仍屬人類最具致命性的惡性疾病之一。因此，為了了解整個腦癌的分子機轉，尋找具代表性的目標基因是必要的。五聚環蛋白–3 ( Pentraxin 3；PTX3)也稱為腫瘤壞死因子誘導性基因14蛋白（TSG-14）基因位於染色體3（q24-28）是五聚環蛋白家族的成員之一，亦屬於發炎蛋白之一，目前已知可能參與細胞凋亡和分化作用，但PTX3在人類神經膠質瘤細胞扮演的角色仍不清楚。本研究利用人類腦癌組織晶片以化學免疫染色法分析證實人類腦癌組織內PTX3蛋白表現比正常腦組織還高，並與腫瘤分化和期數有正相關性。為了釐清PTX3在人類神經膠質瘤細胞細胞的表現，利用西方墨點法發現PTX3在GBM8401細胞中比U251、M059J、Hs683和U87-MG細胞表現還高。為了證實PTX3在GBM8401細胞的生物功能，我們利用shLuc和shPTX3感染GBM8401細胞來抑制內生性PTX3蛋白，分別以細胞存活分析、流式細胞儀和西方墨點法證實抑制PTX3降低細胞生長、誘導細胞週期G0/G1停留。另外我們也證實抑制PTX3會抑制GBM8401細胞移動與侵襲，同時抑制PTX3也會降低MMP-1和MMP-2蛋白量。抑制PTX3也會誘導p38MAPK磷酸化表現增加。綜合以上實驗結果說明PTX3在人類神經膠質瘤細胞的增生與侵襲中扮演了一個重要的角色，且可當作人類神經膠質瘤細胞的指標蛋白。
Malignant glioma is one of the most lethal types of tumor in human. It has been shown that the highly metastasis and invasion result in death of the brain cancer patients. Thus, the find to candidate target genes may be necessary to understand the molecular mechanism of malignant transformation of human glioma tumors. PTX3 called tumor necrosis factor-inducible protein 14 gene (TSG-14) were mapped to chromosomes 24q28.3. PTX3 regulate cell growth, differentiation, invasion and apoptosis have been reported. However, its involvement in human glioma cancer progression remains unclear.To study the role of PTX3 in human malignant brain tumors, immunohistochemical staining from human brain cancer tissue array to found that PTX3 protein expression levels were both significantly upregulated in brain tumor tissues compared with normal brain tissues, and was positively correlated with differentiation (P<0.01) and tumor grade (P<0.01). We found that PTX3 protein expression level was significantly upregulated in GBM8401 cells than other glioma cells (U251, M059J, Hs683, U-87MG). Inhibition of endogenous PTX3 protein expression by using of RNAi assay, and we found that knockdown of PTX3 in GBM8401 cells decreased cell viability and induced cell cycle arrest in G0/G1 phase. Knockdown of PTX3 expression significantly inhibited cell migration and invasion, and inhibited the MMP-1 and MMP-2 expression in human GBM8401 cells. In addition, inhibiting of PTX3 were increased the phosphorylation of p38MAPK in GBM8401 cells.The result will be providing the PTX3 may serve as a tumor marker for poor prognosis for glioma tumor.
