Carbonic Anhydrase II Associated with Plasma Membrane in a Human Pancreatic Duct Cell Line (CAPAN-1)

Alvarez, Laetitia; Fanjul, Marjorie; Carter, Nicholas; Hollande, E

doi:10.1177/002215540104900812

Cited by 22 publications

(13 citation statements)

References 36 publications

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“…In the immunohistochemistry analysis, CA-II expression was localized to the membrane of the tumor endothelium. CA-II may be attached to the inner leaflet of the membrane as shown in a pancreatic cancer cell line (36). However, it is still possible that CA-II expressed in the endothelium is targeted by the immune system because mouse models have shown that immunization with CA-II induced sialoadenitis (37), cholangitis (38), and pancreatitis (39) by targeting CA-II expressed in each organ.…”

Section: Discussionmentioning

confidence: 99%

Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy

Yoshiura¹,

Nakaoka²,

Nishishita³

et al. 2005

Clinical Cancer Research

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Tumor-associated antigens are promising candidates as target molecules for immunotherapy and a wide variety of tumor-associated antigens have been discovered through the presence of serum antibodies in cancer patients.We previously conducted dendritic cell therapy on 10 malignant melanoma patients and shrinkage or disappearance of metastatic tumors with massive necrosis occurred in two patients. In this study, we found a 29-kDa protein against which antibody was elicited by dendritic cell therapy in one of the two patients. Matrix-assisted laser desorption ionization-time of flight/mass spectrometry analysis of the protein isolated by twodimensional electrophoresis combined with Western blots revealed that the 29-kDa protein was carbonic anhydrase II (CA-II). Immunohistochemistry of the tumors and normal tissues showed that CA-II was expressed in the tumor vessel but not in normal vessel endothelium. CA-II expression in tumor endothelium was observed as well in other cancers including esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II expression of normal human vein endothelial cells was significantly up-regulated when cells were cultured in the acidic and hypoxic conditions indicative of a tumor environment. These findings suggest that CA-II is a tumor vessel endothelium^associated antigen in melanoma and other cancers, and elicitation of serum anti^CA-II antibody by dendritic cell therapy may be associated with good clinical outcome including tumor reduction.

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Section: Discussionmentioning

confidence: 99%

Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy

Yoshiura¹,

Nakaoka²,

Nishishita³

et al. 2005

Clinical Cancer Research

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“…We propose that this CA IV could be the extracellular component of an HCO 3 2 transport metabolon in association with cytosolic CA II and HCO 3 2 /Cl 2 exchanger. Indeed, we have described in Capan-1 cells the presence of a CA II associated with the cytosolic leaflet of apical plasma membranes (Alvarez et al 2001), andCheng et al (1998) have proposed the involvement of an apical Cl 2 /HCO 3 2 exchanger in Cl 2 and HCO 3 2 secretion in these cells. The functionality of such a complex has been demonstrated in transfected HEK293 cells (Sterling et al 2002).…”

Section: Discussionmentioning

confidence: 92%

“…The specificity of these two antibodies was established by the absence of cross-reaction with two CA isoforms expressed in Capan-1 cells, CA II Alvarez et al 2001) and CA IX (unpublished data), and by the recognition of a recombinant secreted form of human CA IV, which is normally GPI-anchored, by the CA IV NH 2 antibody and not the CA IV COOH antibody. These two antibodies revealed the presence of two CA IV-immunoreactive proteins with apparent molecular mass of 55 kDa and 35 kDa in Capan-1 cells.…”

Section: Discussionmentioning

confidence: 99%

Expression and Subcellular Localization of a 35-kDa Carbonic Anhydrase IV in a Human Pancreatic Ductal Cell Line (Capan-1)

Fanjul

Alvarez

Hollande

2007

J Histochem Cytochem.

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The high intraluminal concentrations of HCO3− in the human pancreatic ducts have suggested the existence of a membrane protein supplying the Cl−/HCO3− exchanger. Membrane-bound carbonic anhydrase IV (CA IV) is one of the potential candidates for this protein. The difficulties in isolating human pancreatic ducts have led the authors to study the molecular mechanisms of HCO3− secretion in cancerous cell lines. In this work, we have characterized the CA IV expressed in Capan-1 cells. A 35-kDa CA IV was detected in cell homogenates and purified plasma membranes. Treatment of purified plasma membranes with phosphatidylinositol-phospholipase-C indicated that this CA IV was not anchored by a glycosylphosphatidylinositol (GPI). In contrast, its detection on purified plasma membranes by an antibody specifically directed against the carboxyl terminus of human immature GPI-anchored CA IV indicated that it was anchored by a C-terminal hydrophobic segment. Immunoelectron microscopy and double-labeling immunofluorescence revealed that this CA IV was present on apical plasma membranes, and in the rough endoplasmic reticulum, the endoplasmic reticulum-Golgi intermediate compartment, the Golgi complex, and secretory granules, suggesting its transport via the classical biosynthesis/secretory pathway. The expression in Capan-1 cells of a 35-kDa CA IV anchored in the apical plasma membrane through a hydrophobic segment, as is the case in the healthy human pancreas, should make the study of its role in pancreatic HCO3− secretion easier. (J Histochem Cytochem 55: 783–794, 2007)

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“…Recently, experimental evidences have been presented revealing that the CAs might be involved in bone formation [35]. The mammalian CA-II, a cytosolic enzyme, is targeted in intact cell systems under certain physiological conditions to the cell membrane [36–37]. …”

Section: Reviewmentioning

confidence: 99%

“…We have taken this observation as a further indication that carbonate and phosphate deposits are co- or sequentially synthesized onto SaOS-2 cells, during the initial phase of mineral formation. Furthermore, the CA-II has been proven to be (under certain physiological conditions [pH regulation]) localized at the plasma membranes of human pancreatic cells [36], where the enzyme is involved both in pH regulation and in the secretion of bicarbonate through the Cl − /HCO − exchanger [57] and/or an additional HCO 3 − channel [36]. We concluded from the data gathered [20] that the calcium phosphate/HA deposition reactions in bone tissue are preceded by calcium carbonate precipitation, a process that is driven by an increased CA activity (Fig.…”

Section: Reviewmentioning

confidence: 99%

Biocalcite, a multifunctional inorganic polymer: Building block for calcareous sponge spicules and bioseed for the synthesis of calcium phosphate-based bone

Wang¹,

Schröder²,

Müller³

2014

Beilstein J. Nanotechnol.

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SummaryCalcium carbonate is the material that builds up the spicules of the calcareous sponges. Recent results revealed that the calcium carbonate/biocalcite-based spicular skeleton of these animals is formed through an enzymatic mechanism, such as the skeleton of the siliceous sponges, evolutionarily the oldest animals that consist of biosilica. The enzyme that mediates the calcium carbonate deposition has been identified as a carbonic anhydrase (CA) and has been cloned from the calcareous sponge species Sycon raphanus. Calcium carbonate deposits are also found in vertebrate bones besides the main constituent, calcium phosphate/hydroxyapatite (HA). Evidence has been presented that during the initial phase of HA synthesis poorly crystalline carbonated apatite is deposited. Recent data summarized here indicate that during early bone formation calcium carbonate deposits enzymatically formed by CA, act as potential bioseeds for the precipitation of calcium phosphate mineral onto bone-forming osteoblasts. Two different calcium carbonate phases have been found during CA-driven enzymatic calcium carbonate deposition in in vitro assays: calcite crystals and round-shaped vaterite deposits. The CA provides a new target of potential anabolic agents for treatment of bone diseases; a first CA activator stimulating the CA-driven calcium carbonate deposition has been identified. In addition, the CA-driven calcium carbonate crystal formation can be frozen at the vaterite state in the presence of silintaphin-2, an aspartic acid/glutamic acid-rich sponge-specific protein. The discovery that calcium carbonate crystals act as bioseeds in human bone formation may allow the development of novel biomimetic scaffolds for bone tissue engineering. Na-alginate hydrogels, enriched with biosilica, have recently been demonstrated as a suitable matrix to embed bone forming cells for rapid prototyping bioprinting/3D cell printing applications.

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Carbonic Anhydrase II Associated with Plasma Membrane in a Human Pancreatic Duct Cell Line (CAPAN-1)

Cited by 22 publications

References 36 publications

Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy

Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy

Expression and Subcellular Localization of a 35-kDa Carbonic Anhydrase IV in a Human Pancreatic Ductal Cell Line (Capan-1)

Biocalcite, a multifunctional inorganic polymer: Building block for calcareous sponge spicules and bioseed for the synthesis of calcium phosphate-based bone

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