Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion.
Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion.
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DOI：
10.1371/journal.pone.0030219
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Brentnall TA;Lai LA;Coleman J;Bronner MP;Pan S;Chen R
癌症相关的成纤维细胞，由活化的成纤维细胞或肌成纤维细胞组成，存在于实体瘤周围的基质中。这些肌成纤维细胞促进癌细胞的侵袭和转移。调节成纤维细胞的活化和侵袭性肿瘤发生的启动的机制是非常感兴趣的。在许多实体癌周围的基质肌成纤维细胞和侵袭相关基因的表达筛选中，已经检测到细胞骨架蛋白palladin的上调。使用胰腺癌模型，我们研究了外源性palladin在体外正常成纤维细胞中过表达的功能后果及其对肿瘤侵袭早期阶段的影响。Palladin在基质成纤维细胞中的表达发生在肿瘤发生的非常早期。在体内，palladin和肌成纤维细胞标志物α平滑肌肌动蛋白（α-SMA）的一致表达发生在肿瘤周围基质的发育异常阶段早期，并在胰腺肿瘤发生中逐渐增加。在体外将外源性90 kD palladin导入正常人皮肤成纤维细胞（HDF）中可诱导间质成纤维细胞活化为肌成纤维细胞，其标志为α-SMA和波形蛋白的诱导以及细胞形态的物理变化。此外，成纤维细胞中的palladin表达增强了细胞迁移、通过细胞外基质的侵袭和癌细胞可以通过的隧道的产生。成纤维细胞侵袭和隧道的形成是由表达侵袭伪足蛋白和蛋白水解酶的侵袭伪足样细胞突起的发育引起的。正常成纤维细胞与表达k-ras的上皮细胞的共培养触发成纤维细胞中的Palladin表达。总的来说，palladin表达可以赋予肌成纤维细胞特性，进而促进这些肿瘤周围细胞的侵袭潜力，其中侵袭足驱动细胞外基质的降解。成纤维细胞中的Palladin表达可由邻近上皮细胞中的k-ras表达触发。这些数据支持了一个模型，即钯蛋白活化的成纤维细胞促进基质依赖性转移和肿瘤发生上皮的生长。
Cancer-associated fibroblasts, comprised of activated fibroblasts or myofibroblasts, are found in the stroma surrounding solid tumors. These myofibroblasts promote invasion and metastasis of cancer cells. Mechanisms regulating the activation of the fibroblasts and the initiation of invasive tumorigenesis are of great interest. Upregulation of the cytoskeletal protein, palladin, has been detected in the stromal myofibroblasts surrounding many solid cancers and in expression screens for genes involved in invasion. Using a pancreatic cancer model, we investigated the functional consequence of overexpression of exogenous palladin in normal fibroblasts in vitro and its effect on the early stages of tumor invasion. Palladin expression in stromal fibroblasts occurs very early in tumorigenesis. In vivo, concordant expression of palladin and the myofibroblast marker, alpha smooth muscle actin (α-SMA), occurs early at the dysplastic stages in peri-tumoral stroma and progressively increases in pancreatic tumorigenesis. In vitro introduction of exogenous 90 kD palladin into normal human dermal fibroblasts (HDFs) induces activation of stromal fibroblasts into myofibroblasts as marked by induction of α-SMA and vimentin, and through the physical change of cell morphology. Moreover, palladin expression in the fibroblasts enhances cellular migration, invasion through the extracellular matrix, and creation of tunnels through which cancer cells can follow. The fibroblast invasion and creation of tunnels results from the development of invadopodia-like cellular protrusions which express invadopodia proteins and proteolytic enzymes. Palladin expression in fibroblasts is triggered by the co-culture of normal fibroblasts with k-ras-expressing epithelial cells. Overall, palladin expression can impart myofibroblast properties, in turn promoting the invasive potential of these peri-tumoral cells with invadopodia-driven degradation of extracellular matrix. Palladin expression in fibroblasts can be triggered by k-ras expression in adjacent epithelial cells. This data supports a model whereby palladin-activated fibroblasts facilitate stromal-dependent metastasis and outgrowth of tumorigenic epithelium.
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影响因子：
3.5
作者：
Bartsch, D. K.;Langer, P.;Slater, E. P.
通讯作者：
Slater, E. P.
DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
82.9
作者：
Kononen, J;Bubendorf, L;Kallioniemi, OP
通讯作者：
Kallioniemi, OP
影响因子：
7.5
作者：
Gimona, Mario;Buccione, Roberto;Linder, Stefan
通讯作者：
Linder, Stefan
DOI：
10.1158/1055-9965.epi-09-0056
发表时间：
2009-04
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Klein AP;Borges M;Griffith M;Brune K;Hong SM;Omura N;Hruban RH;Goggins M
通讯作者：
Goggins M