Cellular Migration Ability Is Modulated by Extracellular Purines in Ovarian Carcinoma SKOV‐3 Cells

Abstract

Extracellular nucleotides and nucleosides have emerged as important elements regulating tissue homeostasis. Acting through specific receptors, have the ability to control gene expression patterns to direct cellular fate. We observed that SKOV-3 cells express the ectonucleotidases: ectonucleotide pyrophosphatase 1 (ENPP1), ecto-5'-nucleotidase (NT5E), and liver alkaline phosphatase (ALPL). Strikingly, in pulse and chase experiments supplemented with ATP, SKOV-3 cells exhibited low catabolic efficiency in the conversion of ADP into AMP, but they were efficient in converting AMP into adenosine. Since these cells release ATP, we proposed that the conversion of ADP into AMP is a regulatory node associated with the migratory ability and the mesenchymal characteristics shown by SKOV-3 cells under basal conditions. The landscape of gene expression profiles of SKOV-3 cell cultures treated with apyrase or adenosine demonstrated similarities (e.g., decrease FGF16 transcript) and differences (e.g., the negative regulation of Wnt 2, and 10B by adenosine). Thus, in SKOV-3 we analyzed the migratory ability and the expression of epithelium to mesenchymal transition (EMT) markers in response to apyrase. Apyrase-treatment favored the epithelial-like phenotype, as revealed by the re-location of E-cadherin to the cell to cell junctions. Pharmacological approaches strongly suggested that the effect of Apyrase involved the accumulation of extracellular adenosine; this notion was strengthened when the incubation of the SKOV-3 cell with α,β-methylene ADP (CD73 inhibitor) or adenosine deaminase was sufficient to abolish the effect of apyrase on cell migration. Overall, adenosine signaling is a fine tune mechanism in the control of cell phenotype in cancer. J. Cell. Biochem. 118: 4468-4478, 2017. © 2017 Wiley Periodicals, Inc.

Identification and validation of a prognostic index based on a metabolic-genomic landscape analysis of ovarian cancer

“…ENPP1, FH, CYP2E1, HPGDS, ADCY9, NDUFA5, ADH1B and PYGB it characterized in this network. Given the potential molecular mechanisms of the eight MRG, reports on the functions and mechanisms of HPGDS, ADCY9 and NDUFA5 have not been published on OSC [13][14][15][16][17]. However, five of these eight hub MRGs have been studied, namely, ENPP1, FH, CYP2E1, ADH1B and PYGB.…”

“…However, five of these eight hub MRGs have been studied, namely, ENPP1, FH, CYP2E1, ADH1B and PYGB. ENPP1 is increased in ovarian cancer and may promote the migration ability [13]. High level of FH could promote the aggressive and metastatic behaviors.…”

Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CCl4-Treated Fibrotic Mice

“…Microarrays were performed in the Microarray Unit at the Institute of Cellular Physiology (UNAM, CDMX, Mexico). Primary cultures of hepatocytes from control and CCl 4 -treated animals were incubated for 24 h with medium or 100 µM UTP [46]. Briefly, RNA was purified through the Trizol method following the manufacturer's instructions (Thermo Fisher Scientific, Waltham, MA, USA).…”

Purinergic Signaling: A New Regulator of Ovarian Function

“…Interestingly, these ligands exert complementary or antagonistic actions on each other [9]. For example, epithelial-mesenchymal transition (EMT), a cellular plasticity process important in phenotypic programming of metastatic tumors, can be upregulated by ATP in SKOV-3 cells (from ovarian carcinoma) but downregulated by ADO [10]. This circumstance indicates that enzymes (ectonucleotidases) allowing the sequential conversion from ATP to ADO are a potential regulatory node that controls diverse cellular and physiological responses.…”

“…Even though extracellular ADO has not been measured in tumors in vivo, there is evidence that ADO levels increase in tumor microdialysates and are more abundant at the core of the tumor [79]. In vitro studies have also indicated that OCDC-derived cell lines release ATP to the cell medium [10,89].…”