Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients

Abstract

Tumour-associated protein carbonic anhydrase IX (CA IX) has two major forms. One is a cell-associated, transmembrane protein seen on Western blots as a twin band of 54/58 kDa, expressed in gastric mucosa and in several types of cancer. The other is a soluble protein s-CA IX of 50/54 kDa, which is released into the culture medium or into the body fluids, most likely by proteolytic cleavage of the extracellular part from transmembrane and intracellular sequences. While TC media of CA IX-positive tumour cell lines or shortterm cultures of tumour explants contain a relatively high concentration of s-CA IX (20 -50 ng ml À1 ), the level of this antigen in blood serum and urine of renal clear cell carcinoma patients is about 1000 Â lower. The concentration of CA IX in the blood and in urine varies within wide limits and there is no obvious correlation with tumour size. After nephrectomy, s-CA IX is cleared from the blood within a few days. Only an extremely low concentration of CA IX was detectable in the sera and in urine of control individuals.

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer

“…Nevertheless, we showed that the plasma CAIX detected in patients with NSCLC is much lower than CAIX concentrations described in renal cell carcinoma, because the very high constitutive HIF-1a levels in these latter tumours and also differences in CAIX expression depending on the cell type (Li et al, 2008). Increased levels of plasma CAIX have been reported only in urological cancers (Zavada et al, 2003;Li et al, 2008;Hyrsl et al, 2009). Thus, our report is the first study to show evidence of high CAIX levels in the plasma of NSCLC patients.…”

“…This corresponds to the extracellular part of the CAIX molecule, which is composed of the proteoglycan (PG)-like and CA domains that are cleaved off the plasma membrane (Zavada et al, 2003). Our study reports that the plasma CAIX level in NSCLC patients is significantly higher than in healthy individuals (Po0.001).…”

“…CAIX is a multidomain protein consisting in an N-terminal proteoglycan-like (PG) domain, an extracellular catalytic domain (CA), a transmembrane segment (TM) and a C-terminal intracytoplasmic (IC) tail (Hilvo et al, 2008). Recent reports have provided evidence that the extracellular domain of CAIX can be released into body fluids of patients with kidney or bladder cancers and a high CAIX plasma level was associated with poor prognosis in these patients (Zavada et al, 2003;Hyrsl et al, 2009). However, the CAIX plasma level has not yet been evaluated in patients with NSCLC.…”

Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a metalloprotease-dependent process regulated by TACE/ADAM17

“…Its extracellular portion contains a large CA domain, which is N-terminally extended with a proteoglycan (PG)-like region, and via a single-pass transmembrane (TM) region is linked to a short C-terminal intracytoplasmic (IC) tail (Pastorek et al, 1994;Opavsky et al, 1996). The extracellular domain (ECD) of CA IX can be released into the cell culture medium or into the body fluids of tumour patients (Zavada et al, 2003). Concentration of CA IX ECD in the blood and urine varies in a wide range and shows no obvious correlation with the tumour size, at least in patients with renal cell carcinomas.…”

Relation between Carbonic Anhydrase IX Serum Level, Hypoxia and Radiation Resistance of Head and Neck Cancers

“…Túto rozpustnú extracelulárnu doménu CA IX je možné ľahko detekovať v telesných tekutinách pacienta, pomocou metódy ELISA alebo metódou Western blot. Rozpustná forma CA IX sa rýchlo odstraňuje z krvi vylučovaním nezmeneného proteínu do moču a jeho proteolytickou degradáciou [24]. Dôležitým poznatkom je, že v podmienkach hypoxie zostáva rýchlosť bazálneho uvoľňo-vania extracelulárnej domény CA IX nezmenené, a preto zvýšené množstvo CA IX zaznamenané v extracelulárnom priestore a v telesných tekutinách odráža jeho zvýšenú tvorbu v hypoxických bunkách [25].…”