title: Expression and function of the ACE2/angiotensin(1-7)/Mas axis in osteosarcoma cell lines U-2 OS and MNNG-HOS.
abstract: The renin-angiotensin-system (RAS), via its classical angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin II type 1 receptor (AT1R)-axis, is associated with proliferation and metastasis of numerous types of solid tumor. AT1R blockers reduce tumor volume and decrease liver and lung metastasis in murine models of osteosarcoma. Expression and function of the alternative ACE2/Ang(1-7)/Mas axis in osteosarcoma is yet to be studied. In the present study, the basic and interleukin (IL)-1β-stimulated expression of components of this alternative RAS axis were analyzed and the impact of Mas on proliferation and/or migration of U-2 OS and MNNG-HOS osteosarcoma cells was studied. Quantitative polymerase chain reaction revealed that the two cell lines expressed the Ang(1‑7)-generating peptidases ACE2, neutral endopeptidase 24.11 and prolyl-endopeptidase together with the putative receptor for Ang(1-7), Mas. IL-1β provoked an induction of Mas mRNA and protein expression which was associated with a reduction of proliferation and migration. By contrast, small interfering RNA-mediated knockdown of Mas expression led to increased cell proliferation. In conclusion, osteosarcoma cells express a functional active alternative ACE2/Ang(1-7)/Mas axis. The induction and reinforcement of this axis may be beneficial for the treatment of osteosarcoma by reducing growth and preventing cancer metastasis. These effects may be achieved directly by the administration of Mas agonists or, indirectly, via blocking the classical AngII RAS axis via ACE inhibitors or AT1R antagonists.
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, University Medicine Greifswald, Sauerbruchstrasse, Greifswald D-17475, Germany.
authors.forename: Stephan Albrecht
authors.initials: SA
authors.lastname: Ender
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Sauerbruchstrasse, Greifswald D-17475, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dallmer
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Sauerbruchstrasse, Greifswald D-17475, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lässig
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Sauerbruchstrasse, Greifswald D-17475, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Sauerbruchstrasse, Greifswald D-17475, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Wolke
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011945:Receptors, Angiotensin; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2