Endo M, Jain R K, Witwer B, Brown D
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02129, USA.
Microvasc Res. 1999 Sep;58(2):89-98. doi: 10.1006/mvre.1999.2158.
The aquaporins represent a family of transmembrane water channel proteins that are widely distributed in various tissues throughout the body and play a major role in transcellular and transepithelial water movement. Most tumors have been shown to exhibit high vascular permeability and high interstitial fluid pressure, but the transport pathways for water within tumors remain unknown. In this study, we examined the distribution of the aquaporin 1 (AQP1) water channel protein in several types of transplanted tumor. Two mammary carcinomas, MCaIV and R3230AC, and three glioblastomas, HGL21, U87, and F98, were implanted in rats and mice. Two sites of implantation in rodents were chosen: a cranial window (CW) region and a subcutaneous (SC) region. Tissues were studied using immunoblot analysis and immunofluorescence staining. In the mammary carcinomas, AQP1 was localized in vascular structures; no differences between CW and SC regions were observed. Among the three glioblastomas, HGL21 and U87 exhibited similar AQP1 localization in vascular structures, whereas the center of F98 did not show vascular staining. Cell membranes of normal epithelial cells did not show AQP1 expression, while membranes of most tumor cells exhibited significant AQP1 expression. Interestingly, however, HGL21 and F98 in the CW locations showed no AQP1 expression on tumor cell membranes. These results show that the AQP1 water channel is heterogeneously expressed in tumor cells and their vasculature, and that the level of expression is determined not only by the specific cellular origin of the tumor, but also by the location of the tumor in the host animal.
水通道蛋白是一类跨膜水通道蛋白家族，广泛分布于全身各种组织中，在细胞间和上皮间的水转运中起主要作用。大多数肿瘤已被证明具有高血管通透性和高组织液压力，但肿瘤内水的转运途径仍不清楚。在本研究中，我们检测了水通道蛋白1（AQP1）水通道蛋白在几种移植性肿瘤中的分布。将两种乳腺癌MCaIV和R3230AC以及三种胶质母细胞瘤HGL21、U87和F98植入大鼠和小鼠体内。在啮齿动物中选择两个植入部位：颅窗（CW）区域和皮下（SC）区域。使用免疫印迹分析和免疫荧光染色研究组织。在乳腺癌中，AQP1定位于血管结构；未观察到CW和SC区域之间的差异。在三种胶质母细胞瘤中，HGL21和U87在血管结构中表现出相似的AQP1定位，而F98的中心未显示血管染色。正常上皮细胞的细胞膜未显示AQP1表达，而大多数肿瘤细胞的细胞膜表现出显著的AQP1表达。然而，有趣的是，CW部位的HGL21和F98在肿瘤细胞膜上未显示AQP1表达。这些结果表明，AQP1水通道在肿瘤细胞及其脉管系统中呈异质性表达，并且表达水平不仅由肿瘤的特定细胞起源决定，还由肿瘤在宿主动物中的位置决定。
