$ o }: W" K1 f, c2 | f. k(本文来源：网易探索 ) / R% n! m- t. }7 v+ IInvasive three-dimensional organotypic neoplasia from multiple normal human epithelia # F7 s5 g$ w/ t0 V8 LTodd W Ridky,Jennifer M Chow,David J Wong& Paul A $ Y/ R: R! T0 O9 s
Nature Medicine Year published: (2010) DOI: doi:10.1038/nm.2265 7 u m9 f& L5 ~/ n4 r2 I/ U, ~
Received 01 October 2009 Accepted 20 August 2010 Published online 21 November 2010 / u, y8 [" b4 f5 i) z& g
9 E ^. i1 h! l9 F5 DRefined cancer models are required if researchers are to assess the burgeoning number of potential targets for cancer therapeutics in a clinically relevant context that allows a fast turnaround. Here we use tumor-associated genetic pathways to transform primary human epithelial cells from the epidermis, oropharynx, esophagus and cervix into genetically defined tumors in a human three-dimensional (3D) tissue environment that incorporates cell-populated stroma and intact basement membrane. These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through basement membrane, a complex process that is necessary for biological malignancy in 90% of human cancers. Invasion was rapid and was potentiated by stromal cells. Oncogenic signals in 3D tissue, but not 2D culture, resembled gene expression profiles from spontaneous human cancers. We screened 3D organotypic neoplasia with well-characterized signaling pathway inhibitors to distill a clinically faithful cancer gene signature. Multitissue 3D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterizing cancer progression.$ n6 G7 Q9 X6 ^$ B
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3楼原文作者: xiaodiao123 时间: 2010-11-25 13:39
本帖最后由 qingshui1985 于 2010-12-3 12:41 编辑 + `6 V N8 X+ j& V
/ I0 \2 f: V. G! R 回复 xyklmu 的帖子/ `4 R/ e, H6 o! h' @
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您说的很有道理。9 G$ {: h7 C2 s4 Y- w
低等动物干细胞能给人们对于干细胞的起源以及特征很多启发。例如您提到的涡虫smed-p53参与到了干细胞的调控。这在高等动物也是存在的。 , b( I4 y [: Y8 ?* B0 O. H 3 R; g6 A9 L3 t5 l. L; |对于您提及的涡虫干细胞neoblast异质性问题，我觉得现在的细胞或形态学手段是很难解决这一问题的。 $ L1 ]9 L1 d y7 H7 B+ q: ^3 m研究胚胎发育过程中干细胞的分化、人工培养水螅涡虫的胚胎干细胞系，结合干细胞的分子标记，可能对于这个问题的研究有帮助。8 M+ T: \4 Y& F
7 P0 @( s+ k7 @" C# t7 K( q, [关于涡虫上皮组织是否有干细胞。我觉得有必要说一下。三肠目涡虫上皮中无干细胞是有很多证据的。 + B( [+ L' j% N" I+ x4 F6 N1 ~一个很好的标记物是brdu。 - u/ {* ^3 ?) r/ Q" L8 h完整的涡虫被brdu标记后，最初存在于实质组织，然后出现于靠近基膜处，之后3-5天上皮组织就有了brdu。因而干细胞很有可能由实质组织逐步迁移最后穿过了基膜进入上皮组织的。: n$ J; T; \$ S7 u
BrdU-positive cells can be seen throughout the blastemas and within the wound epithelia (arrowheads)。 0 g9 O1 G* G5 u$ G5 ]' ^迁移过程的图片如下：* p. Z; Y l( x
3 [- p [, y! c R( A* l. }[attach]17927[/attach] + m& L2 J7 A4 tCell migration visualized by BrdU labeling. Planarians were fixed at (A) 8 h, (B) 48 h, and (C) ;6 days postfeeding with BrdU5 N1 r! P" T1 v6 A
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[attach]17926[/attach]' E3 e4 j% Y# K- h& n1 ?
(A) Five-day anterior regeneration blastema resulting from amputation 17 h after initial BrdU labeling0 Q- V% q- d0 o( J7 D
文献：[attach]17928[/attach] 0 N2 \, ?$ k* n; \6 X4 N jBromodeoxyuridine specifically labels the regenerative stem cells of planarian # V4 r' \6 w& d7 [: G& nPA Newmark… - Developmental Biology, 2000 ; N: X& a; Y( }8 G
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最后一图是我稍微放大一下。可能与穿越基膜的过程有关。) T" M( v/ i) f0 h$ H; }9 N 作者: cookiezhang 时间: 2010-12-3 16:33