The Cyst Epithelium in Polycystic Kidney Disease Patients Displays Normal Apical-Basolateral Cell Polarity.

The main characteristic of polycystic kidney disease is the development of multiple fluid-filled renal cysts. The discovery of mislocalized sodium-potassium pump (Na,K-ATPase) in the apical membrane of cyst-lining epithelia alluded to reversal of polarity as a possible explanation for the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst-lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical targeting protein Syntaxin-3 also immunolocalized to the apical domain of cyst-lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Thus, no deviations from the typical epithelial distribution of basic cell polarity proteins were observed in the cysts from the six patients. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst-lining epithelia in polycystic kidney disease.

Aquaglyceroporins in Human Breast Cancer.

Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquaglyceroporins also facilitate the transport of glycerol and are thus involved in cellular metabolism. Transcriptomic analysis revealed that the three aquaglyceroporins, AQP3, AQP7 and AQP9, but not AQP10, are overexpressed in human breast cancer. It is, however, unknown if they are all expressed in the same cells or have a heterogeneous expression pattern. To investigate this, we employed immunohistochemical analysis of serial sections from human invasive ductal and lobular breast cancers. We found that AQP3, AQP7 and AQP9 are homogeneously expressed in almost all cells in both premalignant in situ lesions and invasive lesions. Thus, potential intervention strategies targeting cellular metabolism via the aquaglyceroporins should consider all three expressed aquaglyceroporins, namely AQP3, AQP7 and AQP9.

E-cadherin and aquaporin-3 are downregulated in wound edges of human chronic wounds.

Chronic wounds are defined as wounds that fail to proceed through the normal phases of wound healing; a complex process involving different dynamic events including migration of keratinocytes in the epidermis. Chronic wounds are estimated to affect 1-2% of the human population worldwide and are a major socioeconomic burden. The prevalence of chronic wounds is expected to increase with the rising number of elderly and patients with diabetes and obesity, who are at high risk of developing chronic wounds. Since E-cadherin and the water channel aquaporin-3 are important for both skin function and cell migration, and aquaporin-3 is furthermore involved in wound healing of the skin demonstrated by impaired wound healing in aquaporin-3-null mice, we hypothesized that E-cadherin and aquaporin-3 expression may be dysregulated in chronic wounds. Therefore, we investigated the expression of E-cadherin and aquaporin-3 in biopsies from the edges of chronic wounds from human patients. This was accomplished by immunohistochemical stainings of E-cadherin and aquaporin-3 on serial sections followed by qualitative evaluation of staining patterns, which revealed low expression of both E-cadherin and aquaporin-3 at the wound edge. Future studies are needed to reveal if this downregulation is associated with the pathophysiology of chronic wounds.

The cell polarity protein Scribble is downregulated by the water channel aquaporin-5 in breast cancer cells.

Breast carcinomas originate from cells in the terminal duct-lobular unit. Carcinomas are associated with increased cell proliferation and migration, altered cellular adhesion, as well as loss of epithelial polarity. In breast cancer, aberrant and high levels of aquaporin-5 (AQP5) are associated with increased metastasis, poor prognosis, and cancer recurrence. AQP5 increases the proliferation and migration of cancer cells, and ectopic expression of AQP5 in normal epithelial cells reduces cell-cell adhesion and increases cell detachment and dissemination from migrating cell sheets, the latter via AQP5-mediated activation of the Ras pathway. Here, we investigated if AQP5 also affects cellular polarity by examining the relationship between the essential polarity protein Scribble and AQP5. In tissue samples from invasive lobular and ductal carcinomas, the majority of cells with high AQP5 expression displayed low Scribble levels, indicating an inverse relationship. Probing for interactions via a Glutathione S-transferase pull-down experiment revealed that AQP5 and Scribble interacted. Moreover, overexpression of AQP5 in the breast cancer cell line MCF7 reduced both size and circularity of three-dimensional (3-D) spheroids and induced cell detachment and dissemination from migrating cell sheets. In addition, Scribble levels were reduced. An AQP5 mutant cell line, which cannot activate Ras (AQP5S156A) signaling, displayed unchanged spheroid size and circularity and an intermediate level of Scribble, indicating that the effect of AQP5 on Scribble is, at least in part, dependent on AQP5-mediated activation of Ras. Thus, our results suggest that high AQP5 expression negatively regulates the essential polarity protein Scribble and thus, can affect cellular polarity in breast cancer.

Computed tomography-guided radiofrequency ablation is a safe and effective treatment of osteoid osteoma located outside the spine.

INTRODUCTION: The aim of this study was to evaluate the long-term clinical outcome after computed tomography (CT)-guided radiofrequency ablation (RFA) in patients diagnosed with osteoid osteoma (OO) located in the upper and lower extremities. METHODS: The study population included 52 patients with a typical clinical history and radiologically confirmed OO who received CT-guided RFA treatment from 1998 to February 2014 at Aarhus University Hospital, Denmark. The clinical outcome was evaluated based on patient-reported outcome measures and medical record review. RESULTS: The response rate was 52/60 (87%). Pain relief after the first RFA treatment was found in 46/52 (88%) of the patients and after re-RFA in 51/52 (98%) of the patients. One patient underwent open resection after RFA. No major complications occurred, and four patients reported minor complications in terms of small skin burn, minor skin infection and hypoaesthesia at the entry point. In all, 50 of 52 (96%) patients reported to be "very satisfied" with the RFA treatment. CONCLUSION: CT-guided RFA is a safe and effective treatment with high patient satisfaction and it provides robust pain relief and improves the patients' quality of life. RFA should be the treatment of choice for most OO. FUNDING: not relevant. TRIAL REGISTRATION: The Danish Data Protection Agency approved the project with record number 2007-58-0010.