Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells
Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells
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DOI：
10.1038/sj/bjc/6600270
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发表时间：
2002-05-20
影响因子：
8.8
通讯作者：
Jain, RK
中科院分区：
文献类型：
--
作者：
Davies, CD;Berk, DA;Jain, RK
肿瘤细胞外基质充当治疗剂递送的屏障。为了检验细胞外基质成分支配肿瘤组织中大分子的渗透率这一假设，我们测量了三个横纹肌肉瘤亚克隆中非特异性IgG的扩散系数，这些亚克隆在体外生长为多细胞球体，在体内生长为背窗皮下肿瘤。在皮下肿瘤中，扩散系数随着胶原蛋白和硫酸化糖胺聚糖含量的增加而降低。当生长为多细胞球体时，细胞外基质成分或扩散系数均无差异，在体外与体内结果的比较表明，宿主基质细胞在细胞外基质产生中的作用受到肿瘤细胞的调制，因此，治疗性大分子通过肿瘤细胞外基质的渗透可能主要由宿主器官决定。因此，在将药物渗透性从仅由肿瘤细胞组成的球状体和多层细胞夹层外推至体内肿瘤时必须谨慎。
The tumour extracellular matrix acts as a barrier to the delivery of therapeutic agents. To test the hypothesis that extracellular matrix composition governs the penetration rate of macromolecules in tumour tissue, we measured the diffusion coefficient of nonspecific IgG in three rhabdomyosarcoma subclones growing as multicellular spheroids in vitro or as subcutaneous tumours in dorsal windows in vivo. In subcutaneous tumours, the diffusion coefficient decreased with increasing content of collagen and sulphated glycosaminoglycans. When grown as multicellular spheroids, no differences in either extracellular matrix composition or diffusion coefficient were found. Comparison of in vitro vs in vivo results suggests an over riding role of host stromal cells in extracellular matrix production subjected to modulation by tumour cells, Penetration of therapeutic macromolecules through tumour extracellular matrix might thus be largely determined by the host organ. Hence, caution must be exercised in extrapolating drug penetrability from spheroids and multilayer cellular sandwiches consisting of only tumour cells to tumours in vivo.