Hofmann Matthias, Guschel Maike, Bernd August, Bereiter-Hahn Jürgen, Kaufmann Roland, Tandi Christa, Wiig Helge, Kippenberger Stefan
Department of Dermatology and Venerology, University Hospital, Johann Wolfgang Goethe University, Frankfurt/Main D-60590, Germany.
Neoplasia. 2006 Feb;8(2):89-95. doi: 10.1593/neo.05469.
High tumor interstitial fluid pressure (TIFP) is a characteristic of most solid tumors. TIFP may hamper adequate uptake of macromolecular therapeutics in tumor tissue. In addition, TIFP generates mechanical forces affecting the tumor cortex, which might influence the growth parameters of tumor cells. This seems likely as, in other tissues (namely, blood vessels or the skin), mechanical stretch is known to trigger proliferation. Therefore, we hypothesize that TIFP-induced stretch modulates proliferation-associated parameters. Solid epithelial tumors (A431 and A549) were grown in Naval Medical Research Institute nude mice, generating a TIFP of about 10 mm Hg (A431) or 5 mm Hg (A549). Tumor drainage of the central cystic area led to a rapid decline of TIFP, together with visible relaxation of the tumor cortex. It was found by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis that TIFP lowering yields a decreased phosphorylation of proliferation-associated p44/42 mitogen-activated protein kinase and tumor relaxation. In confirmation, immunohistochemical staining showed a decrease of tumor-associated proliferation marker Ki-67 after TIFP lowering. These data suggest that the mechanical stretch induced by TIFP is a positive modulator of tumor proliferation.
高肿瘤间质液压力（TIFP）是大多数实体瘤的一个特征。TIFP可能会阻碍肿瘤组织中大分子治疗药物的充分摄取。此外，TIFP会产生影响肿瘤皮层的机械力，这可能会影响肿瘤细胞的生长参数。这似乎是可能的，因为在其他组织（即血管或皮肤）中，已知机械拉伸会触发增殖。因此，我们假设TIFP诱导的拉伸会调节增殖相关参数。实体上皮肿瘤（A431和A549）在海军医学研究所的裸鼠体内生长，产生约10毫米汞柱（A431）或5毫米汞柱（A549）的TIFP。中央囊性区域的肿瘤引流导致TIFP迅速下降，同时肿瘤皮层明显松弛。通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳和蛋白质印迹分析发现，TIFP降低导致增殖相关的p44/42丝裂原活化蛋白激酶磷酸化减少以及肿瘤松弛。经证实，免疫组织化学染色显示TIFP降低后肿瘤相关增殖标志物Ki-67减少。这些数据表明，TIFP诱导的机械拉伸是肿瘤增殖的正向调节因子。
