title: Reversal of malignant phenotype in human osteosarcoma cells transduced with the alkaline phosphatase gene.
abstract: Alkaline phosphatases are a family of glycoproteins that are able to hydrolize various monophosphate esters at a high pH optimum. Liver/bone/kidney (L/B/K) alkaline phosphatase (ALP) is one of the four major isoenzymes that belong to this family. Apart from its role in normal bone mineralization, other functions of L/B/K ALP remain obscure, both in physiological and in neoplastic conditions, including the bone-forming tumor osteosarcoma. In this study, we transfected the U-2 OS osteosarcoma cell line, which does not show any basal expression of this enzyme, with the full-length gene of L/B/K ALP, and analyzed the in vitro and in vivo features of four transfectants showing different expression of L/B/K ALP. A reduced in vitro ability to invade Matrigel and to grow in a semi-solid medium, together with a lower tumorigenic and metastatic ability in athymic mice, was found to be associated with a high level of cell surface L/B/K ALP activity. Moreover, L/B/K ALP transfectants showed a reduced secretion of matrix metalloproteinase-9 enzyme. These findings indicate a loss of aggressiveness of osteosarcoma cells after the expression of L/B/K ALP on their surface and suggest a new role for this enzyme.
authors.affiliation: Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Manara
authors.forename: N
authors.initials: N
authors.lastname: Baldini
authors.forename: M
authors.initials: M
authors.lastname: Serra
authors.forename: P L
authors.initials: PL
authors.lastname: Lollini
authors.forename: C
authors.initials: C
authors.lastname: De Giovanni
authors.forename: M
authors.initials: M
authors.lastname: Vaccari
authors.forename: A
authors.initials: A
authors.lastname: Argnani
authors.forename: S
authors.initials: S
authors.lastname: Benini
authors.forename: D
authors.initials: D
authors.lastname: Maurici
authors.forename: P
authors.initials: P
authors.lastname: Picci
authors.forename: K
authors.initials: K
authors.lastname: Scotlandi
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D002633:Chemotaxis; D006801:Humans; D051379:Mice; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000469:Alkaline Phosphatase