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

被引:32
作者
Manara, MC
Baldini, N
Serra, M
Lollini, PL
De Giovanni, C
Vaccari, M
Argnani, A
Benini, S
Maurici, D
Picci, P
Scotland, K
机构
[1] Ist Ortoped Rizzoli, Lab Ric Oncol, I-40126 Bologna, Italy
[2] Univ Bologna, Inst Canc, Bologna, Italy
[3] IST, Ist Ric Ric Canc Genova, Unita Satellite Biotecnol, Bologna, Italy
关键词
alkaline phosphatase; osteosarcoma; matrix metalloproteinase; tumorigenicity; metastasis; athymic mice;
D O I
10.1016/S8756-3282(99)00266-5
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 sl;owing 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, (C) 2000 by Elsevier Science Inc. All rights reserved.
引用
收藏
页码:215 / 220
页数:6
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