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- 积分
- 13511
- 威望
- 13511
- 包包
- 32034
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间质支持Stromal Support; t4 @8 p0 P4 |
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肿瘤间质在支持肿瘤生长中起着一个关键性作用(Hu and Polyak, 2008)。越来越明确的是，肿瘤和它的周围间质细胞之间的异型性相互作用引起更好支持肿瘤生长的间质的表现型改变。例如，乳腺癌周围的肌纤维母细胞是由正常的乳腺成纤维细胞分化而来的，它们能分泌基质细胞衍生因子1而剌激肿瘤生长和增加内皮祖细胞而使血管生成 (Orimo et al., 2005)。这个表现型差异从在这些癌相关间质细胞中观察到的重要基因表达和表观遗传变化中得到进一步支持(Allinen et al., 2004)。
7 U; v0 N' i: r& F4 ]& i6 H: ` 另外，已经发现骨髓分化间叶干细胞和造血祖细胞在肿瘤转移中起着重要作用，分别通过细胞因子介导的旁分泌信号或通过它们移动到远处部位以有利于建立转移环境(Kaplan et al., 2005; Karnoub et al., 2007)。虽然肿瘤间质细胞的体细胞突变是罕见的(Allinen et al., 2004; Qiu et al., 2008), 在由NF1基因变异所致的家族性多发性神经纤维瘤病1的病例中，精心设计的鼠模型显示肥大细胞在肿瘤进展中的重要作用。 NF1异质的肥大细胞和骨髓细胞对疾病表现型的贡献依赖于这些细胞中的c-kit信号(可以被迅速伊马替尼抑制的受体)。确实伊马替尼能够成功地应用于减少NF1病人的肿瘤负荷(Yang et al., 2008)，这证实了针对肿瘤非固有的NOA途径的靶向治疗的有效性。我们曾经举压力表现型这个例子来说明NOA，然而认识到其它被抑制时也会与癌生成状态不相容的NOA途径的存在与压力不相关是重要的。
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% l1 w; m6 o9 {9 x8 dStromal Support$ n: l' v1 _3 F! B" D' m i: |( F
The tumor stroma plays a key role in supporting tumor growth (Hu and Polyak, 2008). It is increasingly clear that heterotypic interactions between the tumor and its surrounding stromal cells lead to phenotypic changes in the stroma that better support tumor growth. For example, the yofbroblasts surrounding breast tumors are distinct from normal mammary stromal ! L) r3 C0 } Z
fbroblasts in their ability to secrete stromal-derived factor 1 to both stimulate tumor growth and recruit endothelial progenitor cells for angiogenesis (Orimo et al., 2005). This phenotypic distinction is further supported by substantial gene expression and epigenetic changes observed in these cancer associated 8 W$ n! G3 ~4 x% a2 G& p5 f2 Y9 {
stromal cells (Allinen et al., 2004). In addition, bone marrow-derived mesenchymal stem cells and hematopoietic progenitors have been found to play important roles in tumor metastasis either through cytokine-mediated paracrine signaling or through their mobilization to distal sites to help establish the metastatic niche, respectively (Kaplan et al., 2005; Karnoub et al., 2007). Although somatic mutations in tumor stromal cells are rare (Allinen et al., 2004; Qiu et al., 2008), in the case of familial neurofbromatosis 1 caused by mutations in the NF1 gene, careful modeling of the disease in mice has revealed a striking contribution of mast cells to tumor development. The
6 K1 ~* l. F u% L+ s: t" Wcontribution of NF1 heterozygous mast cells and bone marrow cells to the disease phenotype is dependent on signaling |
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发表于 2011-7-2 15:38
