Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification
Increased metabolism accelerates local acid production in cancer tissue. The mechanisms eliminating acidic waste products from human colon cancer tissue represent promising therapeutic targets for pharmacological manipulation in order to improve prognosis for the increasing number of patients with c...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2019-01-01
|
Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2019/3702783 |
id |
doaj-13dd02e4771f49fca474991565de4e99 |
---|---|
record_format |
Article |
spelling |
doaj-13dd02e4771f49fca474991565de4e992020-11-24T23:47:27ZengHindawi LimitedBioMed Research International2314-61332314-61412019-01-01201910.1155/2019/37027833702783Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular AcidificationNinna C. S. Voss0Henrik Kold-Petersen1Mikkel B. Henningsen2Casper Homilius3Ebbe Boedtkjer4Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Building 1170, DK-8000 Aarhus C, DenmarkRegional Hospital Randers, Skovlyvej 15, DK-8930 Randers, DenmarkDepartment of Biomedicine, Aarhus University, Ole Worms Allé 3, Building 1170, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine, Aarhus University, Ole Worms Allé 3, Building 1170, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine, Aarhus University, Ole Worms Allé 3, Building 1170, DK-8000 Aarhus C, DenmarkIncreased metabolism accelerates local acid production in cancer tissue. The mechanisms eliminating acidic waste products from human colon cancer tissue represent promising therapeutic targets for pharmacological manipulation in order to improve prognosis for the increasing number of patients with colon cancer. We sampled biopsies of human colonic adenocarcinomas and matched normal colon tissue from patients undergoing colon cancer surgery. We measured steady-state intracellular pH and rates of net acid extrusion in freshly isolated human colonic crypts based on fluorescence microscopy. Net acid extrusion was almost entirely (>95%) Na+-dependent. The capacity for net acid extrusion was increased and steady-state intracellular pH elevated around 0.5 in crypts from colon cancer tissue compared with normal colon tissue irrespective of whether they were investigated in the presence or absence of CO2/HCO3–. The accelerated net acid extrusion from the human colon cancer tissue was sensitive to the Na+/H+-exchange inhibitor cariporide. We conclude that enhanced net acid extrusion via Na+/H+-exchange elevates intracellular pH in human colon cancer tissue.http://dx.doi.org/10.1155/2019/3702783 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ninna C. S. Voss Henrik Kold-Petersen Mikkel B. Henningsen Casper Homilius Ebbe Boedtkjer |
spellingShingle |
Ninna C. S. Voss Henrik Kold-Petersen Mikkel B. Henningsen Casper Homilius Ebbe Boedtkjer Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification BioMed Research International |
author_facet |
Ninna C. S. Voss Henrik Kold-Petersen Mikkel B. Henningsen Casper Homilius Ebbe Boedtkjer |
author_sort |
Ninna C. S. Voss |
title |
Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification |
title_short |
Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification |
title_full |
Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification |
title_fullStr |
Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification |
title_full_unstemmed |
Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification |
title_sort |
upregulated na+/h+-exchange protects human colon cancer tissue against intracellular acidification |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2019-01-01 |
description |
Increased metabolism accelerates local acid production in cancer tissue. The mechanisms eliminating acidic waste products from human colon cancer tissue represent promising therapeutic targets for pharmacological manipulation in order to improve prognosis for the increasing number of patients with colon cancer. We sampled biopsies of human colonic adenocarcinomas and matched normal colon tissue from patients undergoing colon cancer surgery. We measured steady-state intracellular pH and rates of net acid extrusion in freshly isolated human colonic crypts based on fluorescence microscopy. Net acid extrusion was almost entirely (>95%) Na+-dependent. The capacity for net acid extrusion was increased and steady-state intracellular pH elevated around 0.5 in crypts from colon cancer tissue compared with normal colon tissue irrespective of whether they were investigated in the presence or absence of CO2/HCO3–. The accelerated net acid extrusion from the human colon cancer tissue was sensitive to the Na+/H+-exchange inhibitor cariporide. We conclude that enhanced net acid extrusion via Na+/H+-exchange elevates intracellular pH in human colon cancer tissue. |
url |
http://dx.doi.org/10.1155/2019/3702783 |
work_keys_str_mv |
AT ninnacsvoss upregulatednahexchangeprotectshumancoloncancertissueagainstintracellularacidification AT henrikkoldpetersen upregulatednahexchangeprotectshumancoloncancertissueagainstintracellularacidification AT mikkelbhenningsen upregulatednahexchangeprotectshumancoloncancertissueagainstintracellularacidification AT casperhomilius upregulatednahexchangeprotectshumancoloncancertissueagainstintracellularacidification AT ebbeboedtkjer upregulatednahexchangeprotectshumancoloncancertissueagainstintracellularacidification |
_version_ |
1725489619539066880 |