Reversal of malignant phenotype in human osteosarcoma cells transduced with the alkaline phosphatase gene

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, ot...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2000-03, Vol.26 (3), p.215-220
Main Authors: Manara, M.C, Baldini, N, Serra, M, Lollini, P.-L, De Giovanni, C, Vaccari, M, Argnani, A, Benini, S, Maurici, D, Picci, P, Scotlandi, K
Format: Article
Language:English
Subjects:
Alkaline phosphatase
Alkaline Phosphatase - genetics
Animals
Athymic mice
Biological and medical sciences
Chemotaxis
Fundamental and applied biological sciences. Psychology
Humans
Matrix metalloproteinase
Metastasis
Mice
Osteosarcoma
Osteosarcoma - enzymology
Osteosarcoma - genetics
Osteosarcoma - pathology
Phenotype
Skeleton and joints
Transduction, Genetic
Tumor Cells, Cultured
Tumorigenicity
Vertebrates: osteoarticular system, musculoskeletal system
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Summary: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.
ISSN:8756-3282
1873-2763
DOI:10.1016/S8756-3282(99)00266-5