title: Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene.
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.
authors.affiliation: Centro di Ricerca in Genetica Molecolare Fondazione Carisbo at the Istituto di Istologia ed Embriologia Generale, University of Bologna, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Zucchini
authors.forename: Michele
authors.initials: M
authors.lastname: Bianchini
authors.forename: Luisa
authors.initials: L
authors.lastname: Valvassori
authors.forename: Stefania
authors.initials: S
authors.lastname: Perdichizzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Benini
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Manara
authors.forename: Rossella
authors.initials: R
authors.lastname: Solmi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Strippoli
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Paolo
authors.initials: P
authors.lastname: Carinci
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D001842:Bone and Bones / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016000:Cluster Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D000469:Alkaline Phosphatase