CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target

Journal of Enzyme Inhibition and Medicinal Chemistry

Claudiu T. Supuran¹  Jakob R. Izbicki²  Morton Freytag²  Astrid Drenckhan²  Stephanie J. Gros³  Guido Sauter⁴ 

[1] Department Neurofarba, Section of Pharmaceutical Sciences, University of Florence, Florence, Italy;Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Pediatric Surgery, Ûniversity Children’s Hospital Basel, Basel, Switzerlan;Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

关键词: Esophageal carcinoma;    hypoxia;    carbonic anhydrase IX;    tumour microenvironment;    targeted therapy;   

DOI  :  10.1080/14756366.2018.1475369

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY