Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.

<h4>Background and purpose</h4>Carbonic anhydrase IX (CAIX) plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl)-ureido)phenyl sulfamate (S4) on the tumor microenvironme...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tineke W H Meijer, Johan Bussink, Miriam Zatovicova, Paul N Span, Jasper Lok, Claudiu T Supuran, Johannes H A M Kaanders
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4c15fb36dd6c4d77a49281544aeece67
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4c15fb36dd6c4d77a49281544aeece67
record_format	dspace
spelling	oai:doaj.org-article:4c15fb36dd6c4d77a49281544aeece672021-11-25T06:00:32ZTumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.1932-620310.1371/journal.pone.0108068https://doaj.org/article/4c15fb36dd6c4d77a49281544aeece672014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108068https://doaj.org/toc/1932-6203<h4>Background and purpose</h4>Carbonic anhydrase IX (CAIX) plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl)-ureido)phenyl sulfamate (S4) on the tumor microenvironment in a laryngeal tumor model by analyzing proliferation, apoptosis, necrosis, hypoxia, metabolism and CAIX ectodomain shedding.<h4>Methods</h4>SCCNij202 tumor bearing-mice were treated with S4 for 1, 3 or 5 days. CAIX ectodomain shedding was measured in the serum after therapy. Effects on tumor cell proliferation, apoptosis, necrosis, hypoxia (pimonidazole) and CAIX were investigated with quantitative immunohistochemistry. Metabolic transporters and enzymes were quantified with qPCR.<h4>Results</h4>CAIX ectodomain shedding decreased after treatment with S4 (p<0.01). S4 therapy did neither influence tumor cell proliferation nor the amount of apoptosis and necrosis. Hypoxia (pimonidazole) and CAIX expression were also not affected by S4. CHOP and MMP9 mRNA as a reference of intracellular pH did not change upon treatment with S4. Compensatory mechanisms of pH homeostasis at the mRNA level were not observed.<h4>Conclusion</h4>As the clinical and biological meaning of the decrease in CAIX ectodomain shedding after S4 therapy is not clear, studies are required to elucidate whether the CAIX ectodomain has a paracrine or autocrine signaling function in cancer biology. S4 did not influence the amount of proliferation, apoptosis, necrosis and hypoxia. Therefore, it is unlikely that S4 can be used as single agent to influence tumor cell kill and proliferation, and to target primary tumor growth.Tineke W H MeijerJohan BussinkMiriam ZatovicovaPaul N SpanJasper LokClaudiu T SupuranJohannes H A M KaandersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e108068 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tineke W H Meijer Johan Bussink Miriam Zatovicova Paul N Span Jasper Lok Claudiu T Supuran Johannes H A M Kaanders Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.
description	<h4>Background and purpose</h4>Carbonic anhydrase IX (CAIX) plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl)-ureido)phenyl sulfamate (S4) on the tumor microenvironment in a laryngeal tumor model by analyzing proliferation, apoptosis, necrosis, hypoxia, metabolism and CAIX ectodomain shedding.<h4>Methods</h4>SCCNij202 tumor bearing-mice were treated with S4 for 1, 3 or 5 days. CAIX ectodomain shedding was measured in the serum after therapy. Effects on tumor cell proliferation, apoptosis, necrosis, hypoxia (pimonidazole) and CAIX were investigated with quantitative immunohistochemistry. Metabolic transporters and enzymes were quantified with qPCR.<h4>Results</h4>CAIX ectodomain shedding decreased after treatment with S4 (p<0.01). S4 therapy did neither influence tumor cell proliferation nor the amount of apoptosis and necrosis. Hypoxia (pimonidazole) and CAIX expression were also not affected by S4. CHOP and MMP9 mRNA as a reference of intracellular pH did not change upon treatment with S4. Compensatory mechanisms of pH homeostasis at the mRNA level were not observed.<h4>Conclusion</h4>As the clinical and biological meaning of the decrease in CAIX ectodomain shedding after S4 therapy is not clear, studies are required to elucidate whether the CAIX ectodomain has a paracrine or autocrine signaling function in cancer biology. S4 did not influence the amount of proliferation, apoptosis, necrosis and hypoxia. Therefore, it is unlikely that S4 can be used as single agent to influence tumor cell kill and proliferation, and to target primary tumor growth.
format	article
author	Tineke W H Meijer Johan Bussink Miriam Zatovicova Paul N Span Jasper Lok Claudiu T Supuran Johannes H A M Kaanders
author_facet	Tineke W H Meijer Johan Bussink Miriam Zatovicova Paul N Span Jasper Lok Claudiu T Supuran Johannes H A M Kaanders
author_sort	Tineke W H Meijer
title	Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.
title_short	Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.
title_full	Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.
title_fullStr	Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.
title_full_unstemmed	Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.
title_sort	tumor microenvironmental changes induced by the sulfamate carbonic anhydrase ix inhibitor s4 in a laryngeal tumor model.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4c15fb36dd6c4d77a49281544aeece67
work_keys_str_mv	AT tinekewhmeijer tumormicroenvironmentalchangesinducedbythesulfamatecarbonicanhydraseixinhibitors4inalaryngealtumormodel AT johanbussink tumormicroenvironmentalchangesinducedbythesulfamatecarbonicanhydraseixinhibitors4inalaryngealtumormodel AT miriamzatovicova tumormicroenvironmentalchangesinducedbythesulfamatecarbonicanhydraseixinhibitors4inalaryngealtumormodel AT paulnspan tumormicroenvironmentalchangesinducedbythesulfamatecarbonicanhydraseixinhibitors4inalaryngealtumormodel AT jasperlok tumormicroenvironmentalchangesinducedbythesulfamatecarbonicanhydraseixinhibitors4inalaryngealtumormodel AT claudiutsupuran tumormicroenvironmentalchangesinducedbythesulfamatecarbonicanhydraseixinhibitors4inalaryngealtumormodel AT johanneshamkaanders tumormicroenvironmentalchangesinducedbythesulfamatecarbonicanhydraseixinhibitors4inalaryngealtumormodel
_version_	1718414278997835776

Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.

Ejemplares similares