Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma
Store-operated Ca2+ entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which sen...
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Format: | Article |
Language: | English |
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Hindawi Limited
2014-01-01
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Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2014/739494 |
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doaj-1b36ce6bae5d4c5d85cbe186140e3915 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Silvia Dragoni Ilaria Turin Umberto Laforenza Duilio Michele Potenza Cinzia Bottino Toma N. Glasnov Martina Prestia Federica Ferulli Anna Saitta Alessandra Mosca Germano Guerra Vittorio Rosti Ombretta Luinetti Carlo Ganini Camillo Porta Paolo Pedrazzoli Franco Tanzi Daniela Montagna Francesco Moccia |
spellingShingle |
Silvia Dragoni Ilaria Turin Umberto Laforenza Duilio Michele Potenza Cinzia Bottino Toma N. Glasnov Martina Prestia Federica Ferulli Anna Saitta Alessandra Mosca Germano Guerra Vittorio Rosti Ombretta Luinetti Carlo Ganini Camillo Porta Paolo Pedrazzoli Franco Tanzi Daniela Montagna Francesco Moccia Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma BioMed Research International |
author_facet |
Silvia Dragoni Ilaria Turin Umberto Laforenza Duilio Michele Potenza Cinzia Bottino Toma N. Glasnov Martina Prestia Federica Ferulli Anna Saitta Alessandra Mosca Germano Guerra Vittorio Rosti Ombretta Luinetti Carlo Ganini Camillo Porta Paolo Pedrazzoli Franco Tanzi Daniela Montagna Francesco Moccia |
author_sort |
Silvia Dragoni |
title |
Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma |
title_short |
Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma |
title_full |
Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma |
title_fullStr |
Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma |
title_full_unstemmed |
Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma |
title_sort |
store-operated ca2+ entry does not control proliferation in primary cultures of human metastatic renal cellular carcinoma |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2014-01-01 |
description |
Store-operated Ca2+ entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca2+ levels within the endoplasmic reticulum (ER) Ca2+ reservoir, and a number of a Ca2+-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1–7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca2+ store, but not by InsP3-dependent Ca2+ release. Metastatic RCC cells express Stim1-2, Orai1–3, and TRPC1–7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 µM Gd3+ and Pyr6, while it was inhibited by 100 µM Gd3+, 2-APB, and carboxyamidotriazole (CAI). Neither Gd3+ nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca2+ signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors. |
url |
http://dx.doi.org/10.1155/2014/739494 |
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doaj-1b36ce6bae5d4c5d85cbe186140e39152020-11-24T20:59:05ZengHindawi LimitedBioMed Research International2314-61332314-61412014-01-01201410.1155/2014/739494739494Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular CarcinomaSilvia Dragoni0Ilaria Turin1Umberto Laforenza2Duilio Michele Potenza3Cinzia Bottino4Toma N. Glasnov5Martina Prestia6Federica Ferulli7Anna Saitta8Alessandra Mosca9Germano Guerra10Vittorio Rosti11Ombretta Luinetti12Carlo Ganini13Camillo Porta14Paolo Pedrazzoli15Franco Tanzi16Daniela Montagna17Francesco Moccia18Department of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Via Forlanini 6, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Via Forlanini 6, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyChristian Doppler Laboratory for Flow Chemistry, Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, 8010 Graz, AustriaDepartment of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Via Forlanini 6, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Via Forlanini 6, 27100 Pavia, ItalyMedical Oncology, “Maggiore della Carità” University Hospital, 28100 Novara, ItalyDepartment of Health Sciences, University of Molise, Via F. de Santis, 86100 Campobasso, ItalyLaboratory of Biotechnology, Center for the Study of Myelofibrosis, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyDepartment of Pathological Anatomy, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyMedical Oncology, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyMedical Oncology, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyMedical Oncology, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Via Forlanini 6, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Via Forlanini 6, 27100 Pavia, ItalyStore-operated Ca2+ entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca2+ levels within the endoplasmic reticulum (ER) Ca2+ reservoir, and a number of a Ca2+-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1–7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca2+ store, but not by InsP3-dependent Ca2+ release. Metastatic RCC cells express Stim1-2, Orai1–3, and TRPC1–7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 µM Gd3+ and Pyr6, while it was inhibited by 100 µM Gd3+, 2-APB, and carboxyamidotriazole (CAI). Neither Gd3+ nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca2+ signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors.http://dx.doi.org/10.1155/2014/739494 |