CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target
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CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target. / Drenckhan, Astrid; Freytag, Morton; Supuran, Claudiu T; Sauter, Guido; Izbicki, Jakob R; Gros, Stephanie J.
in: J ENZYM INHIB MED CH, Jahrgang 33, Nr. 1, 06.2018, S. 1024-1033.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target
AU - Drenckhan, Astrid
AU - Freytag, Morton
AU - Supuran, Claudiu T
AU - Sauter, Guido
AU - Izbicki, Jakob R
AU - Gros, Stephanie J
PY - 2018/6
Y1 - 2018/6
N2 - The hypoxic tumour microenvironment of solid tumours represents an important starting point for modulating progression and metastatic spread. Carbonic anhydrase IX (CAIX) is a known HIF-1α-dependent key player in maintaining cell pH conditions under hypoxia. We show that CAIX is strongly expressed in esophageal carcinoma tissues. We hypothesize that a moderate CAIX expression facilitates metastases and thereby worsens prognosis. Selective inhibition of CAIX by specific CAIX inhibitors and a CAIX knockdown effectively inhibit proliferation and migration in vitro. In the orthotopic esophageal carcinoma model, the humanized HER2 antibody trastuzumab down-regulates CAIX, possibly through CAIX's linkage with HER2 in the hypoxic microenvironment. Our results show CAIX to be an essential part of the tumour microenvironment and a possible master regulator of tumour progression. This makes CAIX a highly effective and feasible therapeutic target for selective cancer treatment.
AB - The hypoxic tumour microenvironment of solid tumours represents an important starting point for modulating progression and metastatic spread. Carbonic anhydrase IX (CAIX) is a known HIF-1α-dependent key player in maintaining cell pH conditions under hypoxia. We show that CAIX is strongly expressed in esophageal carcinoma tissues. We hypothesize that a moderate CAIX expression facilitates metastases and thereby worsens prognosis. Selective inhibition of CAIX by specific CAIX inhibitors and a CAIX knockdown effectively inhibit proliferation and migration in vitro. In the orthotopic esophageal carcinoma model, the humanized HER2 antibody trastuzumab down-regulates CAIX, possibly through CAIX's linkage with HER2 in the hypoxic microenvironment. Our results show CAIX to be an essential part of the tumour microenvironment and a possible master regulator of tumour progression. This makes CAIX a highly effective and feasible therapeutic target for selective cancer treatment.
KW - Antigens, Neoplasm
KW - Antineoplastic Agents
KW - Carbonic Anhydrase IX
KW - Carbonic Anhydrase Inhibitors
KW - Cell Movement
KW - Cell Proliferation
KW - Disease Progression
KW - Dose-Response Relationship, Drug
KW - Drug Screening Assays, Antitumor
KW - Esophageal Neoplasms
KW - Female
KW - Humans
KW - Hypoxia
KW - Male
KW - Middle Aged
KW - Molecular Structure
KW - Structure-Activity Relationship
KW - Tissue Array Analysis
KW - Tumor Cells, Cultured
KW - Tumor Microenvironment
KW - Journal Article
U2 - 10.1080/14756366.2018.1475369
DO - 10.1080/14756366.2018.1475369
M3 - SCORING: Journal article
C2 - 29865880
VL - 33
SP - 1024
EP - 1033
JO - J ENZYM INHIB MED CH
JF - J ENZYM INHIB MED CH
SN - 1475-6366
IS - 1
ER -