title: Increased P2X7 receptor expression and function in thyroid papillary cancer: a new potential marker of the disease?
abstract: Nucleotides are increasingly recognized as nonredundant extracellular signals for chemotaxis, cell growth, and cytokine release. Effects of extracellular nucleotides are mediated by P2 receptors, among which the P2X(7) subtype is attracting increasing attention for its involvement in apoptosis, cell growth, and cytokine release. Recent studies showed that P2X(7) is overexpressed in chronic lymphocytic leukemia and breast and prostate cancer. The aim of the present study was to better understand the clinical significance of P2X(7) receptor expression in normal and cancer human thyroid tissues. P2X(7) receptor message and protein expression and functional activity were tested in two cell lines (FB1 and FB2) established from either anaplastic or papillary primary thyroid cancer and in several histological samples of human papillary cancer. We show here that human thyroid papillary carcinoma, whether of the classical or follicular variant, expresses the P2X(7) receptor (P2X(7)R) to a much higher level than normal thyroid tissue. The P2X(7)R was similarly up-regulated in FB1 and FB2 cell lines. In contrast to normal thyroid cells, both cell lines responded to extracellular nucleotide stimulation with a large increase in intracellular Ca(2+) and secretion of IL-6. Ca(2+) increase was attenuated and release of IL-6 was fully blocked by P2X(7)R inhibitors. Finally, the thyroid carcinoma cell lines had at least a 3-fold higher intracellular ATP concentration and maintained at least a 3-fold higher extracellular ATP level, compared with control cells. These data suggest that an enhanced P2X(7)R function might be a feature of human thyroid cancer.
authors.affiliation: Department of Internal Medicine, University of Pisa, Via Roma 67, I-56100 Pisa, Italy. a.solini@med.unipi.it
authors.forename: Anna
authors.initials: A
authors.lastname: Solini
authors.forename: Sabina
authors.initials: S
authors.lastname: Cuccato
authors.forename: Davide
authors.initials: D
authors.lastname: Ferrari
authors.forename: Eleonora
authors.initials: E
authors.lastname: Santini
authors.forename: Sara
authors.initials: S
authors.lastname: Gulinelli
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Callegari
authors.forename: Angela
authors.initials: A
authors.lastname: Dardano
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Faviana
authors.forename: Stephanie
authors.initials: S
authors.lastname: Madec
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D015850:Interleukin-6; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate