倫敦Queen Mary大學(xué)研究人員發(fā)現(xiàn)一種調(diào)節(jié)胰腺癌細(xì)胞“粘性”的蛋白質(zhì),，研究團(tuán)隊(duì)已經(jīng)表明S100PBP蛋白能抑制蛋白酶Z的水平，蛋白酶Z使胰腺癌細(xì)胞具有粘性,，使得它們能夠擴(kuò)散到周圍環(huán)境中,。
該項(xiàng)研究由英國慈善機(jī)構(gòu),、胰腺癌癥研究基金會(huì)（PCRF的）資助，發(fā)表于《美國病理學(xué)雜志》,。
Queen Mary巴茲癌癥研究所Tatjana Crnogorac-Jurcevic博士說：我們相信這些結(jié)果具有顯著意義,。這些蛋白質(zhì)在調(diào)控胰腺癌細(xì)胞的附著力和侵襲到其他器官的過程中發(fā)揮重要作用，了解了這一點(diǎn)有助于我們開發(fā)新的預(yù)防和治療靶標(biāo),。
該研究小組發(fā)現(xiàn),，蛋白酶Z的生成由S100PBP調(diào)節(jié)。當(dāng)S100PBP大量存在時(shí),，腫瘤細(xì)胞只表達(dá)少量的蛋白酶Z,，蛋白酶Z表達(dá)的減少限制了腫瘤細(xì)胞的蔓延。文章合著者Kate Lines博士研究生表示：團(tuán)隊(duì)希望獲得進(jìn)一步的資金以便在這方面進(jìn)一步開展研究,，我們特別熱衷于找出到底S100PBP是如何調(diào)控蛋白酶Z的水平,。
研究人員希望這些新發(fā)現(xiàn)的蛋白質(zhì)可能最終能開發(fā)出新的療法，可以使患者預(yù)后得到明顯改善,。（生物谷：Bioon）
doi:10.1016/j.ajpath.2011.12.031
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S100P-Binding Protein, S100PBP, Mediates Adhesion through Regulation of Cathepsin Z in Pancreatic Cancer Cells
Kate E. Lines, Claude Chelala, Branko Dmitrovic, Nilukshi Wijesuriya, Hemant M. Kocher, John F. Marshall, Tatjana Crnogorac-Jurcevic
Several S100 proteins are up-regulated in pancreatic ductal adenocarcinoma (PDAC), the most significant being S100P. We previously reported on S100PBP, a binding partner of S100P, that shows no homology to any described protein and whose functions are completely unknown. To determine S100PBP expression across human tissues and organs, immunohistochemistry was performed using both multiorgan- and in-house–constructed pancreatic tissue microarrays. To establish S100PBP functions, cell lines with either stably overexpressed or silenced S100PBP were generated and investigated using Affymetrix gene expression arrays and complementary functional assays. We show that S100PBP is differentially expressed in various healthy and tumor specimens, which is both cancer- and tissue-type dependent. In healthy pancreas, S100PBP is expressed in the nuclear/perinuclear region of both exocrine and endocrine compartments. In early precancerous lesions, S100PBP is translocated to the cytoplasm, whereas in PDAC and metastatic lesions, its expression is significantly diminished. The most pronounced phenotypic change after manipulation of S100PBP expression was seen in adhesion; this was significantly reduced after S100PBP up-regulation and increased after S100PBP silencing. Up-regulation or silencing of S100PBP also led to a concomitant change in the levels of the protease cathepsin Z, the silencing of which significantly reduced PDAC cell adhesion. We further demonstrate that the interaction of cathepsin Z with arginine-glycine-aspartic acid–binding integrins, specifically αvβ5, mediates the changes seen in adhesion of PDAC cells.
