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Signaling Pathways Point To The Weakness Of Breast Cancer Stem Cells6 U! p; S# H6 y4 O& h5 ? l
出处：http://www.healthph.co.cc/2011/06/signaling-pathways-point-to-weakness-of.html: v5 s; A9 H# _6 T* ], d
Friday, June 10, 2011 0 D8 h) g& M$ x2 S |' d
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Whitehead Institute researchers have identified signs of breast epithelial cells can induce these cells to transition and maintain a state of mesenchymal stem cells and cells that pervades normal cells and cancer cells with greater capacity to migrate and renewed itself. Disruption of these tapes indicated the cells self-renewal capacity of migratory, invasive and used by cancer stem cells in tumors of new seeds.9 R" g: }, A" Y; d1 [) E+ H7 _! v
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"Stem cells are important in cancer and normal tissues. On the one hand, we know what creates a type of cancer known as stem cells in tumors and secondly, we want to know what creates normal stem cells in normal epithelial tissues says Whitehead Founding Member Robert Weinberg. "We have reason to believe that these two dynamics are orchestrated by a common regulatory mechanism. Therefore, this work may be applicable for the understanding of breast cancer cells and normal epithelial cells, like normal cells in normal breast ducts. "' j5 Q# \% Q) y
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During epithelial-mesenchymal transition (EMT), epithelial cells acquire the characteristics of mesenchymal cells. Unlike epithelial cells in a very compact that stick to each other, mesenchymal cells are loose and free to move in a tissue. The attributes of mesenchymal cells during development are beneficial, but when hijacked by cancer cells, confer the ability to migrate to remote sites. Moreover, the passage through the EMT allows cells to cancerous tumors in adults new high-yield seeds, the hallmark of cancer stem cells. Passing an EMT is recognized as an important step in the formation of cancer stem cells, scientists have been unable to clearly identify the tracks in the cellular microenvironment that induce EMT.0 `; F# @% X# p
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By examining the human epithelial mammary cells, Christina Scheel, postdoctoral researcher in Weinberg's lab has identified three signaling pathways (TGF-beta, non-canonical Wnts, and canonical Wnts), which together maintain the characteristics of migration and regeneration of both normal mammary epithelium and breast cancer cells. These paths are constantly activated and the stem cells that are autocrine signals, ie signals produced by the cells. Studying how these autocrine signals active in mammary epithelial cells can Scheel clear signals that allow these cells through EMT and then a state of mesenchymal stem cell-like and the first place. Its results will be published June 10 issue of Cell.& ^$ @1 e5 `7 q/ f- {4 C) q
2 ?# v' ^/ G" d T2 [& J+ tInterestingly, Scheel found that epithelial cells, as their state of differentiation through inhibition of the three signaling pathways, that is, of course, normal epithelial cells produce proteins that inhibit these signaling proteins. It pushes the normal mammary epithelial cells through EMT in vitro, has removed these endogenous inhibitors of taking a cocktail of neutralizing antibodies, and added growth factors that stimulate the three courses, which mimics the autocrine signaling was found in mesenchymal cells. Applying the result of EMT-inducing cocktail constantly pushed the mesenchymal cells Scheel and properties stem cell-like state, accompanied by a greater capacity for migratory birds and stem cell-like. Finally, epithelial cells ex stabilized at this space through autocrine signals, and are no longer dependent EMT cocktail.8 X7 l, r1 ?1 M9 a; J/ e
6 h/ I+ \: f! ?If you want to see the effects of autocrine signaling to prevent this animal model, mice implanted Scheel epithelial cells of human breast cancer who had been through EMT. He is injected into the implantation site of proteins that block three routes. The mice were injected with one tenth of the amount of the increase was found in mice that did not receive inhibitory protein. Moreover, in breast cancer cells that had previously been treated in vitro of these proteins is significantly reduced metastases when implanted in mice after.8 B, \4 G& D- I, d H
; m F* Q) t. E+ G: G( T8 |Scheel notes that these tests show that the ability of cancer cells' usurping normal cellular functions may ultimately lead to their downfall.
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# y0 |7 o; d8 ?- e0 S; Y- Z"These autocrine signals may not be something in breast cancer cells to re-invent, but will instead get the activation of a program of normal stem cells," says Scheel. Breast cancer stem cells use these signals to maintain themselves, so they are easy to block this autocrine signaling. It could be a great way to target breast cancer stem cells. In addition, we need to understand how the Migration and self-renewal properties are used in normal mammary epithelial cells, may further our understanding of the homeostasis of normal tissues and can be very useful in the field of regenerative medicine, where it would be highly desirable to create a large number of epithelial stem cells, without use genetic interventions. "
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! A9 |: W" D# \4 uWhile Scheel study provides new information about how well the cancer and normal breast cells, the transition and maintain the state of mesenchymal cells, he and Weinberg are warning that the same signals and signaling pathways may be appealed to the cells of breast.
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"They are the same agents as EMT reporting breast tissue -? Skin, liver, intestines, pancreas, and so on do not know Scheel generalizability of the results yet, although I can not imagine that there are many similarities," says Weinberg, who is also professor of biology at MIT and director of the MIT / Ludwig Center for Molecular Oncology. "Secondly, we do not know if these three signaling pathways are ultimately the ones that are crucial for the activation of EMT as the types of mammary cells. Alternatively, there may be other contextual cues in addition to these three, are equally important in the emergence of EMT as mammalian cells? These signaling pathways appear to be a certain universality, simply do not know. " |
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发表于 2011-6-24 22:58
发表于 2011-6-25 10:07
