Bindels E M, Vermey M, De Both N J, van der Kwast T H
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Virchows Arch. 2001 Oct;439(4):552-9. doi: 10.1007/s004280100419.
To investigate the importance of the microenvironment in bladder cancer invasion, a panel of six bladder carcinoma cell lines (SD, RT112, JON, 1207, T24, and J82) was tested in both in vitro and in vivo invasion assays. Furthermore, invasiveness was correlated with the expression of components of the E-cadherin-catenin complex. The E-cadherin-negative cell lines, T24 and J82, displayed a high in vitro invasive capacity, whereas the E-cadherin-positive cell lines, SD and JON, completely lacked in vitro invasive capacity. In contrast, in vivo invasion was noted for all cell lines, with the exception of cell line JON. Most notably, SD formed highly invasive tumors in vivo. The in vivo invasiveness of the E-cadherin-positive bladder carcinoma cell lines was associated with a heterogeneous expression of the E-cadherin-catenin complex. The discrepancy between in vitro and in vivo invasive behavior implies that, in vivo, the microenvironment plays an important role in the establishment of the invasive phenotype. In addition, it was found that orthotopic xenografting of 1207 and T24 bladder carcinoma cells resulted in site-specific tumor take and an enhanced tumor outgrowth and invasiveness, respectively, compared with heterotopic (i.e., subcutaneous) inoculation. We conclude that the site-specific growth and invasion of the bladder carcinoma cell lines in vivo and the observed assay specific invasion (in vitro vs in vivo) points to an effect of the local (bladder) microenvironment on tumor cell behavior.
为了研究微环境在膀胱癌侵袭中的重要性，我们选用了六种膀胱癌细胞系（SD、RT112、JON、1207、T24和J82）进行体外和体内侵袭实验。此外，侵袭性与E-钙黏蛋白-连环蛋白复合体各成分的表达相关。E-钙黏蛋白阴性的细胞系T24和J82在体外具有较高的侵袭能力，而E-钙黏蛋白阳性的细胞系SD和JON在体外则完全缺乏侵袭能力。相比之下，除JON细胞系外，所有细胞系在体内均有侵袭现象。最值得注意的是，SD在体内形成了高度侵袭性的肿瘤。E-钙黏蛋白阳性的膀胱癌细胞系在体内的侵袭性与E-钙黏蛋白-连环蛋白复合体的异质性表达有关。体外和体内侵袭行为的差异表明，在体内，微环境在侵袭性表型的形成中起着重要作用。此外，研究发现，与异位（即皮下）接种相比，1207和T24膀胱癌细胞原位异种移植分别导致了位点特异性肿瘤形成以及肿瘤生长和侵袭能力增强。我们得出结论，膀胱癌细胞系在体内的位点特异性生长和侵袭以及观察到的实验特异性侵袭（体外与体内）表明局部（膀胱）微环境对肿瘤细胞行为有影响。
