研究人员最近发现了一类新细胞，在癌症发生过程中发挥关键作用。一种高度可变的前癌干细胞（precancerous stem cell，pCSCs），能够根据环境，保持良性状态或恶化。这项发现有助于确定癌症干细胞在疾病恶化和复发过程中扮演的角色，有助于找出预防、诊断和治疗癌症的依据。
现代癌症干细胞理论认为，肿瘤是由多种细胞组成，其中有一小部分就是原始细胞（primitive cells）。它们与人体中的其他干细胞一样，能够自我维持、自我更新，可分化为其他细胞和组织，与普通干细胞不同的是，只要向实验动物注射100个这样的细胞，就有可能引发癌症，因此这种细胞得名癌症干细胞（cancer stem cells）。
癌症干细胞最初是从白血病中分离出来的，之前的实验发现，它们在乳腺癌、脑癌、结肠癌和睾丸癌中也存在。极度不稳定的特性使它们很难被分离和描述。它们能够抵抗所有治疗，有些研究人员认为它们是癌症复发的原因。
俄亥俄州立大学医学院Jian-Xin Gao博士率领的研究小组，最近鉴别出一组新的前癌干细胞。这些细胞与已经发育成熟的癌症干细胞有些相似，但对不同的细胞信号做出反应，决定最终的命运，继续生长为癌症还是成为癌症干细胞，保持未活化的状态，还是被人体的免疫系统清除。
这些前癌干细胞既不携带Sca-1和c-kit标记（正常骨髓干细胞的特征），也不携带大多数癌症细胞所具有的标记，只是表达干细胞的结构。研究人员推测这些不寻常的细胞是前癌干细胞。这些细胞非常复杂。它们有正常干细胞和异常干细胞的功能，并不一定会引发癌症。只是偶尔，并且在非常特别的条件下，才会引发癌症，这些细胞似乎是一类新的细胞，与癌症发生有关。
此外，研究人员选择了三个pCSC细胞株，将它们分别注射到三组小鼠的皮下组织、腹腔膜或经脉中，这些实验小鼠的免疫功能不同。研究结果显示，免疫系统的强度决定了小鼠是否发生癌症。
英文原文：
New Cell Type Identified in Cancer Development
Scientists have discovered a new type of cell that appears to play a role in the development of cancer ?a highly volatile, precancerous stem cell that can either remain benign or become malignant, depending upon environmental cues. The finding may help define the role of cancer stem cells in the growth and recurrence of the disease as well as offer new options for cancer prevention, detection and treatment.
Current cancer stem cell theory holds that tumors are comprised of a variety of cell types. Among them is a small subset of rather primitive cells that, like other stem cells in the body, are self-sustaining, self-renewing and multipotent, or capable of creating other types of cells and tissues. These cells are different from normal stem cells, however, in that injecting even as few as 100 of them into laboratory animals will cause cancer. Scientists have dubbed these cancer stem cells.
Cancer stem cells were first identified in leukemia, but they have also been found in breast, brain, colon and prostate cancers. Because they are rather unstable, they are notoriously tricky to isolate and describe. They are also resistant to virtually any kind of treatment, and some scientists believe they are the reason cancer recurs. Until now, no one has known how they arise.
But a team of scientists, led by Dr. Jian-Xin Gao, a researcher in the department of pathology at Ohio State University Medical Center, has identified a new set of cells he calls precancerous stem cells (pCSCs).
These cells share some of the characteristics full-fledged cancer stem cells have, but they are different in that they respond to distinct cell signals that determine their ultimate fate ?whether they will continue to grow into cancer or cancer stem cells, lie inactive or be eradicated by the body抯 immune system.
"These hybrid cells are very complex. They have properties of normal and abnormal stem cells, and do not always lead to cancer ?only some of the time, and under very specific conditions," says Gao, who is also a member of the Ohio State University Comprehensive Cancer Center. "These cells appear to be a whole new class of cells involved in the development of cancer."
The study appears in the Wednesday, March 21 edition of PLoS ONE, the international, peer-reviewed, open-access, online publication from the Public Library of Science (PLoS).
The findings emerged from a study in which Gao and his colleagues were investigating tumor growth in mice. They discovered that some of the animals had lymphoma, and that several cell lines from those tumors carried a unique and provocative phenotype, or surface protein signature: They carried neither the Sca-1 or c-kit markers, hallmarks of normal bone marrow stem cells, nor the lineage markers most of the cancer cells had, but they did exhibit stem-like structure. The researchers suspected these unusual cells might be precancerous stems cells and designed several tests and experiments to find out more about them.
They selected three pCSC lines and injected them subcutaneously, intraperitoneally or intravenously into three groups of mice. The mice represented different levels of immune function: One group was comprised of severe combined immune deficient mice, a second group was composed of mice whose immune systems had been knocked out by radiation, but had been partially restored by an infusion of bone marrow cells; and the third group was made up of normal, healthy mice.
The results showed that the strength of the immune system affected whether or not the mice got cancer. The scientists found that the pCSCs, like normal stem cells, had the ability to create various types of benign cells in mice with healthy or recovering immune systems. These daughter cells, however, were likely to die, especially when they encountered signals to further differentiate ?a strong contrast to the behavior of normal stem cells.
"We thought this was an interesting development," says Gao, "because these precancerous cells were actually stopped from becoming malignant. We are calling this process 慸ifferentiation-induced cell death,?a protective mechanism the body may invoke to prevent pCSCs from maturing into full-blown cancer stem cells."
It was a different story with the mice with impaired immune systems, however. In those animals, the pCSCs developed into solid tumors, developing additional mutations in different cell types as they grew and spread.
Additional experiments revealed that the piwil2 gene may exclusively regulate the process of pCSC development.
Gao says these data suggest some important characteristics of pCSCs. "First, it appears that pCSCs require some sort of signal, or cue, from their immediate environment that directs them to become benign or malignant. Second, it seems clear that they can be detected and eliminated by a robust immune system when they are actively developing into cancer cells."
Cancer stem cell theory is still in its infancy, but Gao feels these findings, if validated by additional studies, point to a candidate population of precancerous cells that may one day be a valuable target for new drugs and treatments. "To cure cancer, we have to eliminate all potential malignant cells ?not just the ones within easy reach."
Source: Public Library of Science
http://www.bio.com/newsfeatures/ ... .jhtml?cid=27100020
