美國(guó)得克薩斯州大學(xué)西南醫(yī)學(xué)中心和達(dá)拉斯兒童醫(yī)學(xué)中心的研究人員發(fā)現(xiàn),，成熟的肌肉纖維（而不是臨近的未成熟細(xì)胞）能夠變成惡性的軟組織癌,。這種癌癥專(zhuān)門(mén)襲擊兒童和青少年,。
該研究組進(jìn)行的果蠅實(shí)驗(yàn)不但為癌癥如何產(chǎn)生問(wèn)題提供重要線索,，而且還意味著研究人員能夠利用果蠅來(lái)研究其他與癌癥有關(guān)的基因,。
在此之前,，還沒(méi)有任何動(dòng)物模型系統(tǒng)證實(shí)過(guò)新的細(xì)胞能夠由已經(jīng)分化的骨骼肌所產(chǎn)生,。骨骼肌一直被認(rèn)為在生物學(xué)上是非常穩(wěn)固的，因此這個(gè)新發(fā)現(xiàn)令研究人員非常驚訝,，并顛覆了這種長(zhǎng)久以來(lái)的觀點(diǎn),。這項(xiàng)研究的結(jié)果刊登在9月5日的《美國(guó)科學(xué)院院刊》上。
研究人員主要研究了腺泡狀橫紋肌肉瘤（Alveolar Rhabdomyosarcoma）——一種橫紋肌肉瘤亞型,，是第六大兒童癌癥,。腺泡狀橫紋肌肉瘤是一種侵略性、致死性的癌癥,，主要發(fā)生在軀干,、胳膊和腿部。
當(dāng)兩種基因PAX3和PAX7中的一個(gè)基因與另外一個(gè)叫做FKHR的基因發(fā)生融合時(shí)就會(huì)引發(fā)這種疾病,。但是,，目前研究人員還不知道哪種類(lèi)型的組織變成了腫瘤細(xì)胞,，是成熟的肌肉細(xì)胞還是圍繞著成熟細(xì)胞的不完全成熟細(xì)胞。
腫瘤細(xì)胞通常只有一個(gè)細(xì)胞核,，而發(fā)育成熟的肌肉組織則含有多達(dá)幾百個(gè)細(xì)胞核,。肌細(xì)胞被衛(wèi)星細(xì)胞所環(huán)繞，這些衛(wèi)星細(xì)胞能夠發(fā)育成成熟肌肉細(xì)胞,，這些細(xì)胞只含有一個(gè)細(xì)胞核,。肌肉和衛(wèi)星細(xì)胞又被類(lèi)似成體干細(xì)胞的細(xì)胞所包圍。
研究人員通過(guò)基因工程手段讓果蠅的幼蟲(chóng)含有人類(lèi)的PAX-FKHR基因復(fù)合體,。他們利用這種昆蟲(chóng)的原因是因?yàn)樗募∪夂苋菀淄高^(guò)外殼看到,。這些基因與另外一個(gè)基因連接在一起，這個(gè)基因使細(xì)胞在PAX-FKHR基因活動(dòng)時(shí)顯示出綠色光,。
他們分析了PAX7-FKHR復(fù)合體和PAX3-FKHR復(fù)合體果蠅,。兩種基因復(fù)合體都創(chuàng)造出與腺泡狀橫紋肌肉瘤雷塞的致死性狀態(tài)。因技術(shù)原因,，研究人員接著對(duì)PAX7-FKHR進(jìn)行了特別研究,，并看到從完全分化的肌肉組織中產(chǎn)生了新的細(xì)胞。他們還看到幼蟲(chóng)血液,、中樞神經(jīng)系統(tǒng)和其他位點(diǎn)中的腫瘤細(xì)胞——這意味著細(xì)胞能自由活動(dòng)和轉(zhuǎn)移,。
由于人類(lèi)和果蠅基因幾乎是相同的，因此果蠅還可能用來(lái)檢測(cè)其他與癌癥有關(guān)的基因,，即在果蠅中敲除這些基因,，然后看是否對(duì)癌癥的形成產(chǎn)生影響。
英文原文：
Mature Muscle Fibers Can Revert to Become Cancerous
Mature muscle fibers, rather than their less-developed neighbors, are the tissues that turn malignant in a soft-tissue cancer that strikes children and teens, researchers at UT Southwestern Medical Center and Children's Medical Center Dallas have found.
The research, performed in fruit flies, not only provides a clue to how the cancer arises, but also means that scientists can use the flies to search for other genes involved in the cancer.
"Never before has any animal model system shown that new cells can be generated from differentiated skeletal muscle," said Dr. Rene Galindo, lead author of the study, assistant professor of pathology at UT Southwestern and a pediatric pathologist at Children's.
"Skeletal muscle had been viewed as being biologically fixed," he said.
The research is available online and is being published in the Sept. 5 issue of the Proceedings of the National Academy of Sciences.
The researchers focused on alveolar rhabdomyosarcoma, a subtype of rhabdomyosarcoma, the sixth most common childhood cancer. Alveolar rhabdomyosarcoma is an aggressive, often fatal form of cancer that occurs primarily in the trunk, arms and legs of older children or teenagers.
The disease starts when one of two genes, called PAX3 and PAX7, fuses with another gene called FKHR, or "Forkhead."
Scientists, however, had not known which type of tissue turned into tumor cells: mature muscle cells or the more immature cells that surround or form them. The question arose partly because of the number of nuclei found in each cell.
The tumor cells each have a single nucleus, while developed muscle tissue contains many nuclei - up to several hundred. The muscle cells are surrounded by satellite cells, which can develop into mature muscle cells, each having a single nucleus. Both muscle and satellite cells are in turn surrounded by adult stem cell-like cells.
The researchers used larvae of the fruit fly Drosophila and genetically engineered them to contain human PAX-FKHR gene complexes. The scientists used the insect because its muscles are easily visible through its outer shell. The genes were linked with another gene that made cells glow green if the PAX-FKHR genes were active.
They examined flies with both the PAX7-FKHR complex and PAX3-FKHR complex. Both gene complexes created fatal conditions similar to alveolar rhabdomyosarcoma. For technical reasons, the researchers then focused on PAX7-FKHR, and saw new cells arising from the fully developed muscle tissue. They also saw tumor cells in the larvae's blood, central nervous system and other locations, indicating that the cells had broken free and metastasized.
Because human and fly genes are nearly identical, it should be possible to test for other genes involved in the cancer by knocking them out, then seeing if that deletion blocks the creation of the cancer.
"We can test virtually every gene in the fly genome," Dr. Galindo said.
"There has been little progress toward developing effective therapies for rhabdomyosarcoma, in part because of the lack of animal models for the disease," said Dr. Eric Olson, chairman of molecular biology at UT Southwestern and the study's senior author. "This work is important because it provides a simple organism, the fruit fly, as a model for analyzing the genetic causes of rhabdomyosarcoma."
"Second, it reveals a fascinating biological process in which a human gene for rhabdomyosarcoma causes skeletal muscle fibers to undergo a reverse form of development and generate single cells that spread through the organism," said Dr. Olson, director of the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and director of the Nearburg Family Center for Basic Research in Pediatric Oncology.
UT Southwestern research technician Jay Allport also participated in the study.
The work was supported by the Society for Pediatric Pathology, the UT Southwestern President's Research Council, the UT Southwestern Physician Scientist Training Program, the National Institutes of Health, the Donald W. Reynolds Cardiovascular Clinical Research Center, the Robert A. Welch Foundation and the Nearburg Foundation.
