南加州大學Keck醫(yī)學院的一項研究發(fā)現(xiàn),，一種使乳腺癌細胞避過身體先天免疫反應(yīng)的蛋白質(zhì)還可能成為將來癌癥藥物的一個靶標,。這項研究的結(jié)果刊登在7月1日的American Journal of Pathology雜志上。研究首次確定出細胞表面上的EphB4蛋白如何起作用。
這項研究暗示，如果我們能將蛋白質(zhì)EphB4關(guān)閉，那么腫瘤細胞就會死亡,，即這種蛋白質(zhì)的功能是幫助癌細胞存活。
研究人員將一種熒光染料附著在這種蛋白質(zhì)的抗體上以確定這種蛋白質(zhì)在腫瘤細胞上的定位,。研究人員的第一步是要確定出這種蛋白質(zhì)在癌細胞上的位置以及出現(xiàn)的頻率,。結(jié)果，他們發(fā)現(xiàn)這種蛋白質(zhì)在60％的腫瘤上都存在,，并且它在癌癥發(fā)生的最初階段就被表達,。
接著，研究人員著手確定EphB4的功能,。他們發(fā)現(xiàn)EphB4蛋白質(zhì)能夠充當一個崗哨,，保護腫瘤細胞不受來自身體的對腫瘤的任何防御攻擊。
攜帶這種蛋白質(zhì)的腫瘤細胞能與附近的血管進行交流,。它給血管發(fā)信號,，促其生長。
將來的抗癌藥物或許能通過抑制這種蛋白質(zhì),，來干掉腫瘤細胞的一個衛(wèi)兵,。利用相似的思路，人們已經(jīng)開發(fā)出了第一個乳腺癌生物治療藥物——Herceptin,。Herceptin能靶向her2蛋白質(zhì)——這種蛋白存在于20%的腫瘤細胞表面,。
Her2蛋白也在這項研究中起到一定的作用。這種蛋白質(zhì)和它的幾個兄弟蛋白能夠活化EphB4,。目前,，研究人員正在深入研究這種蛋白質(zhì)在癌細胞中如何被開啟和關(guān)閉。
英文：
A protein that allows breast cancer cells to evade the body’s natural immune responses could be a target of future cancer therapies, according to a study by Keck School of Medicine of USC scientists published today.
The study, published in the July 1 issue of the American Journal of Pathology, is the first to identify how EphB4 – a protein that sits on the surface of cells – functions.
“The important aspect of this study is that … if we turn the protein [EphB4] off, the tumor cells die, which means that its function helps the cancer cells survive,” says Parkash S. Gill, MD, a professor of medicine in the Keck School the study’s senior author.
The scientists used a fluorescent dye attached to the protein’s antibody to reveal the protein’s location on the tumor cells.
“The first step was to identify whether it’s there [on cancer cells] and how often,” he explained. “We found that it was present on 60 percent of the tumors … and it’s expressed from the very first stage of the cancer formation.”
The next step was to determine EphB4’s purpose. What the scientists discovered was that EphB4 serves as a sentry, guarding the tumor cells from any defenses the body deploys to attack them.
“There are means in the body to kill tumor cells,” Gill says. “[If] you block those then you give the cells the opportunity to survive and grow.” Not only did EphB4 block those defenses, but it helped the cancer cells flourish by issuing a call for more blood vessels – the biological equivalent of food for the tumor.
“The tumor cell carrying this protein … on its surface communicates with blood vessels nearby,” Gill says. “It sends the signal for more blood vessels to grow. One key item for any cancer to grow is to include more blood vessels.”
The goal of a future anti-cancer therapy would be to block the protein, essentially knocking out one of the tumor cell’s guardians. A similar approach was used to develop Herceptin, one of the first biological treatments for breast cancer. Herceptin targets the her2 protein, which is found on the surface of tumor cells about 20 percent of the time, says Gill.
The her2 protein played a role in this study as well. That protein, along with several of its cousins, was found to activate EphB4, he said. “There are certain growth factors that can make this particular protein (EphB4) go up,” Gill says. “We are learning more about how this protein is turned on and off in a cancer cell.”
The other Keck School researchers and study’s authors were S. Ram Kumar, Jasbir Singh, Guangbin Xia, Eric J. Ley, Jeffrey Scehnet, Neil G. Kumar, Debra Hawes, Michael F. Press and Fred A. Weaver. Valery Krasnoperov and Loubna Hassanieh from VasGene Inc. also contributed to the paper.
The study was funded by the Entertainment Industry Foundation’s Women’s Cancer Research Fund and the National Institutes of Health.
