Heterogeneous expression of the aquaporin 1 (AQP1) water channel in tumors of the prostate, breast, ovary, colon and lung: A study using high density multiple human tumor tissue microarrays

Author(s):  
Ali Mobasheri ◽  
Rachel Airley ◽  
Stephen Hewitt ◽  
David Marples
2021 ◽  
Vol 118 (7) ◽  
pp. e2018690118
Author(s):  
François Moisan ◽  
Sandra Oucherif ◽  
Priscilla Kaulanjan-Checkmodine ◽  
Sorilla Prey ◽  
Benoît Rousseau ◽  
...  

Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at nontoxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition, and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 down-regulation trigger the same pathway, suggesting that AQP1 is a major driver of beta-blocker antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TCs). Functional in vitro studies showed that AQP1-positive TCs play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel-based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely, at least in part, on a cross talk between lesional vascular cells and stromal TCs.


1997 ◽  
Vol 272 (5) ◽  
pp. F579-F586 ◽  
Author(s):  
T. L. Pallone ◽  
M. R. Turner

Molecular sieving of small solutes by outer medullary descending vasa recta (OMDVR). Descending vasa recta (DVR) plasma equilibrates with the medullary interstitium by volume efflux (Jv), as well as by influx of solutes. Jv is driven by transmural osmotic pressure gradients due to small hydrophilic solutes (delta pi s), NaCl and urea. DVR endothelium probably contains a "water-only" pathway most likely mediated by the aquaporin-1 (AQP1) water channel. We measured the ability of microperfused OMDVR to concentrate lumenal 22Na and [3H]raffinose when Jv was driven by transmural NaCl gradients. Collectate-to-perfusate ratios of 2 x 10(6) M(r) fluorescein isothiocyanate-labeled dextran volume marker (RDx), 22Na (RNa), and [3H]raffinose (Rraf) were measured in the absence and presence of Jv. During volume efflux (Jv > 0), RDx was 1.37 +/- 0.31. RNa increased from 0.64 +/- 0.03 when Jv = 0 to 0.82 +/- 0.05 when Jv > 0 and Rraf increased from 0.83 +/- 0.03 to 1.13 +/- 0.05: Mathematical simulations predict RNa and Rraf most accurately when the OMDVR reflection coefficient to the tracers is assigned a value near unity. This indicates that the OMDVR wall contains a pathway for osmotic volume flux that excludes small hydrophilic solutes, a behavior consistent with that of aquaporins.


2014 ◽  
Vol 306 (1) ◽  
pp. F123-F129 ◽  
Author(s):  
C. Michele Nawata ◽  
Kristen K. Evans ◽  
William H. Dantzler ◽  
Thomas L. Pannabecker

To better understand the role that water and urea fluxes play in the urine concentrating mechanism, we determined transepithelial osmotic water permeability ( Pf) and urea permeability ( Purea) in isolated perfused Munich-Wistar rat long-loop descending thin limbs (DTLs) and ascending thin limbs (ATLs). Thin limbs were isolated either from 0.5 to 2.5 mm below the outer medulla (upper inner medulla) or from the terminal 2.5 mm of the inner medulla. Segment types were characterized on the basis of structural features and gene expression levels of the water channel aquaporin 1, which was high in the upper DTL (DTLupper), absent in the lower DTL (DTLlower), and absent in ATLs, and the Cl-1 channel ClCK1, which was absent in DTLs and high in ATLs. DTLupper Pf was high (3,204.5 ± 450.3 μm/s), whereas DTLlower showed very little or no osmotic Pf (207.8 ± 241.3 μm/s). Munich-Wistar rat ATLs have previously been shown to exhibit no Pf. DTLupper Purea was 40.0 ± 7.3 × 10−5 cm/s and much higher in DTLlower (203.8 ± 30.3 × 10−5 cm/s), upper ATL (203.8 ± 35.7 × 10−5 cm/s), and lower ATL (265.1 ± 49.8 × 10−5 cm/s). Phloretin (0.25 mM) did not reduce DTLupper Purea, suggesting that Purea is not due to urea transporter UT-A2, which is expressed in short-loop DTLs and short portions of some inner medullary DTLs close to the outer medulla. In summary, Purea is similar in all segments having no osmotic Pf but is significantly lower in DTLupper, a segment having high osmotic Pf. These data are inconsistent with the passive mechanism as originally proposed.


2002 ◽  
Vol 65 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Junichi KAMIIE ◽  
Masaki NAMETA ◽  
Meilei MA ◽  
Takuma TAKATA ◽  
Hidehiko FUJINAKA ◽  
...  

2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.


1994 ◽  
Vol 65 (4) ◽  
pp. 243-246 ◽  
Author(s):  
P.M.T. Deen ◽  
D.O. Weghuis ◽  
Geurts van Kessel ◽  
B. Wieringa ◽  
C.H. van Os
Keyword(s):  

2002 ◽  
Vol 87 (6) ◽  
pp. 621-623 ◽  
Author(s):  
S Saadoun ◽  
M C Papadopoulos ◽  
D C Davies ◽  
B A Bell ◽  
S Krishna

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