Abstract:
: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.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Drenckhan A,Freytag M,Supuran CT,Sauter G,Izbicki JR,Gros SJdoi
10.1080/14756366.2018.1475369subject
Has Abstractpub_date
2018-12-01 00:00:00pages
1024-1033issue
1eissn
1475-6366issn
1475-6374journal_volume
33pub_type
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