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

M. C. Manara, N. Baldini, M. Serra, P. L. Lollini, C. De Giovanni, M. Vaccari, A. Argnani, S. Benini, D. Maurici, P. Picci, K. Scotlandi

Research output: Contribution to journalArticlepeer-review

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. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)215-220
Number of pages6
JournalBone
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 2000

Keywords

  • Alkaline phosphatase
  • Athymic mice
  • Matrix metalloproteinase
  • Metastasis
  • Osteosarcoma
  • Tumorigenicity

ASJC Scopus subject areas

  • Physiology
  • Hematology

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