Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene

Cinzia Zucchini, Michele Bianchini, Luisa Valvassori, Stefania Perdichizzi, Stefania Benini, Maria Cristina Manara, Rossella Solmi, Pierluigi Strippoli, Piero Picci, Paolo Carinci, Katia Scotlandi

Research output: Contribution to journalArticlepeer-review

Abstract

Alkaline phosphatases (ALPs) are a family of cell surface glycoproteins that catalyze the hydrolysis of phosphomonoesters with release of inorganic phosphate. Liver/bone/kidney (L/B/K) ALP participates in bone mineralization, but its other physiological and pathological functions remain obscure. In human osteosarcoma, an inverse relationship has been found between cellular L/B/K ALP expression and aggressiveness. To explore this relationship, we employed cDNA microarray technology to characterize and compare the gene expression profile of two U-2 OS osteosarcoma clones with high L/B/K ALP activity (U-2/ALP28 and U-2/ALP40) and one with contrasting characteristics (U-2/ALP23). We identified 79 differentially expressed genes (58 upregulated in U-2/ALP28 and U-2/ALP40 compared to U-2/ALP23). Using GenMAPP/MAPPFinder, we highlighted nine functional groups strictly related to high L/B/K ALP activity, including microtubule-based movement and cell adhesion groups, two functions well related to tumor invasiveness. Notably, cadherin 13 (CDH13) and caveolin 1 (CAV1) genes were upregulated in our cells. Since these two genes are involved in cell-cell adhesion and cell growth, their co-expression with L/B/K ALP could help explain the lower levels of malignancy found in osteosarcoma cells with high L/B/K ALP activity. Although functional studies are needed to better define the role of CDH13 and CAV1 in the malignant behavior of osteosarcoma cells, the data presented here provide an aid to understanding the biological functions of L/B/ K ALP in bone tumors.

Original languageEnglish
Pages (from-to)672-679
Number of pages8
JournalBone
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 2004

Keywords

  • Alkaline phosphatase
  • Cadherin 13
  • Caveolin 1
  • cDNA microarrays
  • Osteosarcoma

ASJC Scopus subject areas

  • Physiology
  • Hematology

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