Influence of AQP1 on cell adhesion, migration, and tumor sphere formation in malignant pleural mesothelioma is substratum- and histological-type dependent

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer. MPM cells express aquaporin-1 (AQP1) that in other cancers has been shown to participate in the tumor metastasis processes. However, in MPM patients AQP1 overexpression is an independent prognostic factor favoring survival. In this study we aimed at evaluating the role of AQP1 in cell adhesion, migration, and tumor sphere formation in nonmalignant mesothelial cells (MeT-5A) and in epithelioid (M14K) and sarcomatoid (ZL34) MPM cell lines. We used fibronectin (FN) or homologous cell-derived extracellular martrix (ECM) substratum to investigate the role of AQP1 in these experimental phenotypes, inhibiting AQP1 by 10(-5) M mercury chloride (MC). Deposited ECM during cell culture exhibited significant concentration differences among cell types. ZL34 cell adhesion was significantly higher than MeT-5A or M14K cells on FN and ECM. MeT-5A and M14K cell adhesion on FN was sensitive to AQP1 inhibition, whereas AQP1 inhibition on ECM was limited to M14K cells. Wound healing in ZL34 cells was significantly higher than MeT-5A and M14K cells on FN and ECM. AQP1 inhibition significantly lowered cell migration in ZL34 cells on FN and ECM. Sphere formation was not dependent on FN or ECM in the media. AQP1 inhibition in FN media reduced sphere formation in M14K cells, whereas, in ECM, all three cell types were sensitive to AQP1 inhibition.

Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas

“…It may be that the retained expression of AQP1 in MM relates to a degree of preserved differentiation, while complete loss (as in most of the sarcomatoid MMs) indicates a lesser level of mesothelial differentiation and enhanced aggressiveness. However it is worth noting that, like other tumours, inhibition of AQP1 by either synthetic blocker or siRNA resulted in decreased MM cell motility and invasiveness in standard culture and spheres [ 14 , 23 ]. However, AQP1 is also expressed by vascular endothelial cells, and blockade of AQP1 disrupts vessel formation in a number of models [ 24 , 25 , 26 ].…”

Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report

“…AQP1 is a water channel protein found in cell membranes throughout the body and facilitates transcellular water transport [ 7 , 8 ]. In MPM cases, AQP1 has a role in cell proliferation, adhesion and motility, as well as in the modulation of pleural fluid volumes [ 9 , 10 , 11 , 12 ]. Furthermore, an increased expression of AQP1 evaluated by immunohistochemistry in asbestos-related MPM has been documented as a possible predictor of better prognosis.…”

Protective potential of miR-146a-5p and its underlying molecular mechanism in diverse cancers: a comprehensive meta-analysis and bioinformatics analysis

“…Previous studies have revealed the positive regulation of AQP1 in tumor progression and demonstrated that AQP1 suppressors could repress biological activities of various tumors, including the growth of tumor cells, cell motility, and angiogenesis [94,95]. Positive correlations between AQP1 expression and tumor development have been detected in cancers of the reproductive system (ovarian cancer [96] and prostate cancer [97]), digestive system (cancers of the stomach [98], colon [99], and esophagus [100]), and other systems (astrocytoma [101], and cancers of the lung [102], breast [103,104], bladder [105], and pleura [106]). In our study, the high expression of AQP1 in lung cancer was proved by RT-qPCR, contrasting with low miR-146a-5p levels in lung cancer tissues in previous work [25], which strengthened the reliability of our prediction results and implied that AQP1 might be a target of miR-146a-5p in diverse cancers, especially lung cancer.…”