Role of extracellular matrix assembly in interstitial transport in solid tumors.
Role of extracellular matrix assembly in interstitial transport in solid tumors.
复制标题
DOI：
--
复制
发表时间：
2000-05
期刊：
影响因子：
11.2
通讯作者：
P. Netti;D. Berk;M. Swartz;A. Grodzinsky;R. Jain
中科院分区：
文献类型：
--
作者：
P. Netti;D. Berk;M. Swartz;A. Grodzinsky;R. Jain
细胞外基质（ECM）可能通过阻止治疗剂的渗透而有助于实体肿瘤的耐药。我们测量了四种肿瘤类型间质对大分子（IgG）运动的抗性差异，发现运输抗性与机械刚度之间存在意想不到的对应关系。光漂白后原位荧光重分布测定IgG间质扩散系数。组织弹性模量和水力导电性测量由封闭压缩切除组织。与现有的范式明显矛盾的是，这些功能特性与胶原蛋白的总组织含量相关，而不是糖胺聚糖。在抗穿透性较强的肿瘤中观察到一个扩展的胶原网络。抗穿透性越强的肿瘤，胶原酶治疗可显著提高IgG间质扩散率。我们得出结论，胶原蛋白影响组织对大分子运输的抵抗力，可能是通过结合和稳定ECM的糖胺聚糖成分。这些发现提示了一种新的方法来筛选肿瘤对基于大分子的治疗的潜在抗性。此外，胶原蛋白和胶原蛋白-多糖键被认为是改善大分子传递的潜在治疗靶点。
The extracellular matrix (ECM) may contribute to the drug resistance of a solid tumor by preventing the penetration of therapeutic agents. We measured differences in interstitial resistance to macromolecule (IgG) motion in four tumor types and found an unexpected correspondence between transport resistance and the mechanical stiffness. The interstitial diffusion coefficient of IgG was measured in situ by fluorescence redistribution after photobleaching. Tissue elastic modulus and hydraulic conductivity were measured by confined compression of excised tissue. In apparent contradiction to an existing paradigm, these functional properties are correlated with total tissue content of collagen, not glycosaminoglycan. An extended collagen network was observed in the more penetration-resistant tumors. Collagenase treatment of the more penetration-resistant tumors significantly increased the IgG interstitial diffusion rate. We conclude that collagen influences the tissue resistance to macromolecule transport, possibly by binding and stabilizing the glycosaminoglycan component of the ECM. These findings suggest a new method to screen tumors for potential resistance to macromolecule-based therapy. Moreover, collagen and collagen-proteoglycan bonds are identified as potential targets of treatment to improve macromolecule delivery.