title: 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.
authors.affiliation: Faculty of Medicine, Department of Physiology, University of Thessaly, Biopolis, Larissa, Greece; and.
authors.forename: Rajesh M
authors.initials: RM
authors.lastname: Jagirdar
authors.affiliation: Faculty of Medicine, Department of Physiology, University of Thessaly, Biopolis, Larissa, Greece; and.
authors.forename: Eleni
authors.initials: E
authors.lastname: Apostolidou
authors.affiliation: Faculty of Medicine, Department of Physiology, University of Thessaly, Biopolis, Larissa, Greece; and.
authors.forename: Paschalis Adam
authors.initials: PA
authors.lastname: Molyvdas
authors.affiliation: Faculty of Medicine, Department of Respiratory Medicine, University of Thessaly, Biopolis, Larissa, Greece.
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Gourgoulianis
authors.affiliation: Faculty of Medicine, Department of Physiology, University of Thessaly, Biopolis, Larissa, Greece; and Faculty of Medicine, Department of Respiratory Medicine, University of Thessaly, Biopolis, Larissa, Greece.
authors.forename: Chrissi
authors.initials: C
authors.lastname: Hatzoglou
authors.affiliation: Faculty of Medicine, Department of Physiology, University of Thessaly, Biopolis, Larissa, Greece; and Faculty of Medicine, Department of Respiratory Medicine, University of Thessaly, Biopolis, Larissa, Greece szarog@med.uth.gr.
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Zarogiannis
mesh_terms: D051398:Aquaporin 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008627:Mercuric Chloride / Q000494:pharmacology; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D010997:Pleural Neoplasms / Q000378:metabolism* / Q000473:pathology; D018874:Spheroids, Cellular / Q000378:metabolism*
chemical_list: C496020:AQP1 protein, human; D005353:Fibronectins; D051398:Aquaporin 1; D008627:Mercuric Chloride
keywords: aquaporin-1; cell adhesion; cell migration; malignant pleural mesothelioma; tumor sphere formation