Critical Role of Aquaporins in Cancer: Focus on Hematological Malignancies

SIMPLE SUMMARY: Aquaporins are proteins able to regulate the transfer of water and other small substances such as ions, glycerol, urea, and hydrogen peroxide across cellular membranes. AQPs provide for a huge variety of physiological phenomena; their alteration provokes several types of pathologies including cancer and hematological malignancies. Our review presents data revealing the possibility of employing aquaporins as biomarkers in patients with hematological malignancies and evaluates the possibility that interfering with the expression of aquaporins could represent an effective treatment for hematological malignancies. ABSTRACT: Aquaporins are transmembrane molecules regulating the transfer of water and other compounds such as ions, glycerol, urea, and hydrogen peroxide. Their alteration has been reported in several conditions such as cancer. Tumor progression might be enhanced by aquaporins in modifying tumor angiogenesis, cell volume adaptation, proteases activity, cell–matrix adhesions, actin cytoskeleton, epithelial–mesenchymal transitions, and acting on several signaling pathways facilitating cancer progression. Close connections have also been identified between the aquaporins and hematological malignancies. However, it is difficult to identify a unique action exerted by aquaporins in different hemopathies, and each aquaporin has specific effects that vary according to the class of aquaporin examined and to the different neoplastic cells. However, the expression of aquaporins is altered in cell cultures and in patients with acute and chronic myeloid leukemia, in lymphoproliferative diseases and in multiple myeloma, and the different expression of aquaporins seems to be able to influence the efficacy of treatment and could have a prognostic significance, as greater expression of aquaporins is correlated to improved overall survival in leukemia patients. Finally, we assessed the possibility that modifying the aquaporin expression using aquaporin-targeting regulators, specific monoclonal antibodies, and even aquaporin gene transfer could represent an effective therapy of hematological malignancies.