南加州大学Keck医学院的一项研究发现,一种使乳腺癌细胞避过身体先天免疫反应的蛋白质还可能成为将来癌症药物的一个靶标。这项研究的结果刊登在7月1日的American Journal of Pathology杂志上。研究首次确定出细胞表面上的EphB4蛋白如何起作用。
这项研究暗示,如果我们能将蛋白质EphB4关闭,那么肿瘤细胞就会死亡,即这种蛋白质的功能是帮助癌细胞存活。
研究人员将一种荧光染料附着在这种蛋白质的抗体上以确定这种蛋白质在肿瘤细胞上的定位。研究人员的第一步是要确定出这种蛋白质在癌细胞上的位置以及出现的频率。结果,他们发现这种蛋白质在60%的肿瘤上都存在,并且它在癌症发生的最初阶段就被表达。
接着,研究人员着手确定EphB4的功能。他们发现EphB4蛋白质能够充当一个岗哨,保护肿瘤细胞不受来自身体的对肿瘤的任何防御攻击。
携带这种蛋白质的肿瘤细胞能与附近的血管进行交流。它给血管发信号,促其生长。
将来的抗癌药物或许能通过抑制这种蛋白质,来干掉肿瘤细胞的一个卫兵。利用相似的思路,人们已经开发出了第一个乳腺癌生物治疗药物——Herceptin。Herceptin能靶向her2蛋白质——这种蛋白存在于20%的肿瘤细胞表面。
Her2蛋白也在这项研究中起到一定的作用。这种蛋白质和它的几个兄弟蛋白能够活化EphB4。目前,研究人员正在深入研究这种蛋白质在癌细胞中如何被开启和关闭。
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.