美國斯坦福大學(xué)醫(yī)學(xué)院研究人員日前發(fā)現(xiàn)一種對胰腺癌生長至關(guān)重要的蛋白質(zhì),，抑制這種蛋白質(zhì)的表達(dá)可以顯著放緩甚至阻止胰腺腫瘤的生長,。
這種蛋白質(zhì)名為CCN2,，是一種結(jié)締組織生長因子,。研究人員將CCN2表達(dá)水平各異的人類胰腺癌細(xì)胞注入不同實(shí)驗(yàn)鼠的皮下后發(fā)現(xiàn),，CCN2表達(dá)水平較高的胰腺癌細(xì)胞生長迅速,，而CCN2表達(dá)被抑制的胰腺癌細(xì)胞基本不能在實(shí)驗(yàn)鼠體內(nèi)生成腫瘤,。
研究人員還發(fā)現(xiàn)，CCN2表達(dá)水平較高的癌細(xì)胞比表達(dá)水平低的癌細(xì)胞生長和轉(zhuǎn)移速度都快,，注射前種癌細(xì)胞的實(shí)驗(yàn)鼠很快就不治而死,。
研究人員說,，實(shí)體胰腺腫瘤常常會面對缺氧狀況,，此時(shí)腫瘤細(xì)胞會通過一系列信號來調(diào)節(jié)多種基因并促進(jìn)腫瘤血管生成，使腫瘤細(xì)胞在適應(yīng)缺氧微環(huán)境的同時(shí),，引起腫瘤自身的侵襲性增加以及對放射治療的抵抗性增加,。研究人員推測，CCN2可能在這一過程中發(fā)揮了重要作用,。
研究人員表示,，他們希望利用這項(xiàng)成果開發(fā)出治療人類胰腺癌的新方法。這一成果已刊登在最新一期美國《癌癥研究》雜志上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Research 69, 775-784, February 1, 2009. doi: 10.1158/0008-5472.CAN-08-0987
The Role of Tumor Cell–Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth
Kevin L. Bennewith1, Xin Huang1, Christine M. Ham1,2, Edward E. Graves1, Janine T. Erler1, Neeraja Kambham3, Jonathan Feazell1, George P. Yang2, Albert Koong1 and Amato J. Giaccia1
Departments of 1 Radiation Oncology, 2 Surgery, and 3 Pathology, Stanford University School of Medicine, Stanford, California
Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA–expressing clones showed dramatically reduced growth in soft agar and when implanted s.c. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by positron emission tomography imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed colocalization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell–derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer.
