title: The inhibition of aromatase alters the mechanical and rheological properties of non-small-cell lung cancer cell lines affecting cell migration.
abstract: Tumor invasion and metastasis are key aspects of non-small cell lung cancer (NSCLC). During migration, cells undergo mechanical alterations. The mechanical phenotype of breast cancer cells is correlated with aromatase gene expression. We have previously shown that targeting aromatase is a promising strategy for NSCLC. The aim of this study was to examine morphological and mechanical changes of NSCLC cells, upon treatment with aromatase inhibitor and correlate their ability to migrate and invade. In vitro experiments were performed using H23 and A549 NSCLC cell lines and exemestane was used for aromatase inhibition. We demonstrated that exemestane reduced H23 cell migration and invasion and caused changes in cell morphology including increased vacuolar structures and greater pleomorphism. In addition, exemestane changed the distribution of α-tubulin in H23 and A549 cells in a way that might destabilize microtubules polymerization. These effects were associated with increased cell viscosity and decreased elastic shear modulus. Although exemestane caused similar effects in A549 cells regarding viscosity and elastic shear modulus, it did not affect A549 cell migration and caused an increase in invasion. The increased invasion was in line with vimentin perinuclear localization. Our data show that the treatment of NSCLC cells with an aromatase inhibitor not only affects cell migration and invasion but also alters the mechanical properties of the cells. It suggests that the different origin of cancer cells is associated with different morphological characteristics and mechanical behavior.
authors.affiliation: Clinical Oncology laboratory, Division of Oncology, Department of Medicine, University of Patras, Rion, Patra 26504, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Giannopoulou
authors.affiliation: Clinical Oncology laboratory, Division of Oncology, Department of Medicine, University of Patras, Rion, Patra 26504, Greece.
authors.forename: K E
authors.initials: KE
authors.lastname: Siatis
authors.affiliation: Laboratory of Biomechanics and Biomedical Engineering, Department of Mechanical Engineering and Aeronautics, University of Patras, Rion, Patra 26504, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Metsiou
authors.affiliation: Clinical Oncology laboratory, Division of Oncology, Department of Medicine, University of Patras, Rion, Patra 26504, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Kritikou
authors.affiliation: Department of Anatomy-Histology-Embryology, Unit of Bone and Soft Tissue Studies, Department of Medicine, University of Patras, Rion, 26504, Greece.
authors.forename: D J
authors.initials: DJ
authors.lastname: Papachristou
authors.affiliation: Clinical Oncology laboratory, Division of Oncology, Department of Medicine, University of Patras, Rion, Patra 26504, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Kalofonou
authors.affiliation: Clinical Oncology laboratory, Division of Oncology, Department of Medicine, University of Patras, Rion, Patra 26504, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Koutras
authors.affiliation: Laboratory of Biomechanics and Biomedical Engineering, Department of Mechanical Engineering and Aeronautics, University of Patras, Rion, Patra 26504, Greece. Electronic address: gathan@mech.upatras.gr.
authors.forename: G
authors.initials: G
authors.lastname: Athanassiou
authors.affiliation: Clinical Oncology laboratory, Division of Oncology, Department of Medicine, University of Patras, Rion, Patra 26504, Greece. Electronic address: kalofonos@upatras.gr.
authors.forename: H P
authors.initials: HP
authors.lastname: Kalofonos
mesh_terms: D000199:Actins / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001696:Biomechanical Phenomena / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D009361:Neoplasm Invasiveness; D012212:Rheology / Q000187:drug effects*; D014404:Tubulin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D000730:Androstadienes; D047072:Aromatase Inhibitors; D014404:Tubulin; D014746:Vimentin; D001141:Aromatase; C056516:exemestane
keywords: Aromatase; Mechanical properties; Migration; Non-small-cell lung cancer cell