研究人員最近發(fā)現(xiàn)了一類新細(xì)胞,，在癌癥發(fā)生過程中發(fā)揮關(guān)鍵作用,。一種高度可變的前癌干細(xì)胞（precancerous stem cell，pCSCs）,，能夠根據(jù)環(huán)境,，保持良性狀態(tài)或惡化。這項(xiàng)發(fā)現(xiàn)有助于確定癌癥干細(xì)胞在疾病惡化和復(fù)發(fā)過程中扮演的角色,，有助于找出預(yù)防,、診斷和治療癌癥的依據(jù)。
現(xiàn)代癌癥干細(xì)胞理論認(rèn)為,，腫瘤是由多種細(xì)胞組成,，其中有一小部分就是原始細(xì)胞（primitive cells）。它們與人體中的其他干細(xì)胞一樣,，能夠自我維持,、自我更新，可分化為其他細(xì)胞和組織,，與普通干細(xì)胞不同的是,，只要向?qū)嶒?yàn)動(dòng)物注射100個(gè)這樣的細(xì)胞，就有可能引發(fā)癌癥,，因此這種細(xì)胞得名癌癥干細(xì)胞（cancer stem cells）,。
癌癥干細(xì)胞最初是從白血病中分離出來(lái)的，之前的實(shí)驗(yàn)發(fā)現(xiàn),，它們?cè)谌橄侔?、腦癌、結(jié)腸癌和睪丸癌中也存在,。極度不穩(wěn)定的特性使它們很難被分離和描述,。它們能夠抵抗所有治療，有些研究人員認(rèn)為它們是癌癥復(fù)發(fā)的原因,。
俄亥俄州立大學(xué)醫(yī)學(xué)院Jian-Xin Gao博士率領(lǐng)的研究小組,，最近鑒別出一組新的前癌干細(xì)胞。這些細(xì)胞與已經(jīng)發(fā)育成熟的癌癥干細(xì)胞有些相似,，但對(duì)不同的細(xì)胞信號(hào)做出反應(yīng),，決定最終的命運(yùn)，繼續(xù)生長(zhǎng)為癌癥還是成為癌癥干細(xì)胞,，保持未活化的狀態(tài),，還是被人體的免疫系統(tǒng)清除。
這些前癌干細(xì)胞既不攜帶Sca-1和c-kit標(biāo)記（正常骨髓干細(xì)胞的特征）,，也不攜帶大多數(shù)癌癥細(xì)胞所具有的標(biāo)記,，只是表達(dá)干細(xì)胞的結(jié)構(gòu),。研究人員推測(cè)這些不尋常的細(xì)胞是前癌干細(xì)胞。這些細(xì)胞非常復(fù)雜,。它們有正常干細(xì)胞和異常干細(xì)胞的功能,，并不一定會(huì)引發(fā)癌癥。只是偶爾,，并且在非常特別的條件下,，才會(huì)引發(fā)癌癥，這些細(xì)胞似乎是一類新的細(xì)胞,，與癌癥發(fā)生有關(guān),。
此外，研究人員選擇了三個(gè)pCSC細(xì)胞株,，將它們分別注射到三組小鼠的皮下組織,、腹腔膜或經(jīng)脈中，這些實(shí)驗(yàn)小鼠的免疫功能不同,。研究結(jié)果顯示,，免疫系統(tǒng)的強(qiáng)度決定了小鼠是否發(fā)生癌癥。
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
