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, 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.
Manara
M C
MC
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
Baldini
N
N
Serra
M
M
Lollini
P L
PL
De Giovanni
C
C
Vaccari
M
M
Argnani
A
A
Benini
S
S
Maurici
D
D
Picci
P
P
Scotlandi
K
K
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
D000469:Alkaline Phosphatase