美国得克萨斯州大学西南医学中心和达拉斯儿童医学中心的研究人员发现，成熟的肌肉纤维（而不是临近的未成熟细胞）能够变成恶性的软组织癌。这种癌症专门袭击儿童和青少年。
该研究组进行的果蝇实验不但为癌症如何产生问题提供重要线索，而且还意味着研究人员能够利用果蝇来研究其他与癌症有关的基因。
在此之前，还没有任何动物模型系统证实过新的细胞能够由已经分化的骨骼肌所产生。骨骼肌一直被认为在生物学上是非常稳固的，因此这个新发现令研究人员非常惊讶，并颠覆了这种长久以来的观点。这项研究的结果刊登在9月5日的《美国科学院院刊》上。
研究人员主要研究了腺泡状横纹肌肉瘤（Alveolar Rhabdomyosarcoma）——一种横纹肌肉瘤亚型，是第六大儿童癌症。腺泡状横纹肌肉瘤是一种侵略性、致死性的癌症，主要发生在躯干、胳膊和腿部。
当两种基因PAX3和PAX7中的一个基因与另外一个叫做FKHR的基因发生融合时就会引发这种疾病。但是，目前研究人员还不知道哪种类型的组织变成了肿瘤细胞，是成熟的肌肉细胞还是围绕着成熟细胞的不完全成熟细胞。
肿瘤细胞通常只有一个细胞核，而发育成熟的肌肉组织则含有多达几百个细胞核。肌细胞被卫星细胞所环绕，这些卫星细胞能够发育成成熟肌肉细胞，这些细胞只含有一个细胞核。肌肉和卫星细胞又被类似成体干细胞的细胞所包围。
研究人员通过基因工程手段让果蝇的幼虫含有人类的PAX-FKHR基因复合体。他们利用这种昆虫的原因是因为它的肌肉很容易透过外壳看到。这些基因与另外一个基因连接在一起，这个基因使细胞在PAX-FKHR基因活动时显示出绿色光。
他们分析了PAX7-FKHR复合体和PAX3-FKHR复合体果蝇。两种基因复合体都创造出与腺泡状横纹肌肉瘤雷塞的致死性状态。因技术原因，研究人员接着对PAX7-FKHR进行了特别研究，并看到从完全分化的肌肉组织中产生了新的细胞。他们还看到幼虫血液、中枢神经系统和其他位点中的肿瘤细胞——这意味着细胞能自由活动和转移。
由于人类和果蝇基因几乎是相同的，因此果蝇还可能用来检测其他与癌症有关的基因，即在果蝇中敲除这些基因，然后看是否对癌症的形成产生影响。
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.
