Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma
Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma
复制标题
胶原蛋白结合蛋白多糖纤维蛋白可确定实验性癌症的基质结构和体液平衡
DOI：
10.1073/pnas.0702014104
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发表时间：
2007-08-28
影响因子：
11.1
通讯作者：
Rubin, Kristofer
中科院分区：
文献类型：
--
作者：
Oldberg, Ake;Kalamajski, Sebastian;Rubin, Kristofer
对肿瘤基质生物学的研究有可能导致开发更有效的治疗方案，提高基于药物治疗实体恶性肿瘤的疗效。肿瘤间质的特征是血管扭曲，激活的结缔组织细胞产生富含胶原的基质，并伴有间质液压力（IFP）升高，表明肿瘤组织和血液之间存在运输障碍。在这里，我们发现胶原结合蛋白多糖纤维调节蛋白控制实验性癌的基质结构和体液平衡。基因消融或抗炎药物抑制表达表明纤维调节素促进致密间质形成和IFP升高。纤维调素缺乏不影响血管，但增加细胞外液容量，降低IFP。我们的数据表明，纤维调节素控制基质结构，从而调节基质内部和外部的流体对流。这一发现尤其重要，因为有针对性地调节癌症中的体液平衡可以增加对癌症治疗剂的反应。
Research on the biology of the tumor stroma has the potential to lead to development of more effective treatment regimes enhancing the efficacy of drug-based treatment of solid malignancies. Tumor stroma is characterized by distorted blood vessels and activated connective tissue cells producing a collagen-rich matrix, which is accompanied by elevated interstitial fluid pressure (IFP), indicating a transport barrier between tumor tissue and blood. Here, we show that the collagen-binding proteoglycan fibromodulin controls stroma structure and fluid balance in experimental carcinoma. Gene ablation or inhibition of expression by anti-inflammatory agents showed that fibromodulin promoted the formation of a dense stroma and an elevated IFP. Fibromodulin-deficiency did not affect vasculature but increased the extracellular fluid volume and lowered IFP. Our data suggest that fibromodulin controls stroma matrix structure that in turn modulates fluid convection inside and out of the stroma. This finding is particularly important in relation to the demonstration that targeted modulations of the fluid balance in carcinoma can increase the response to cancer therapeutic agents.