RESUMEN
BACKGROUND: To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue. METHODS: The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters. RESULTS: Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = - 0.354; p = 0.013), D'Amico risk stratification (ρ = - 0.336; p = 0.012), ISUP grade (ρ = - 0.321; p = 0.017) and Gleason score (ρ = - 0.342; p = 0.011). CONCLUSIONS: This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.
Asunto(s)
Acuaporinas/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Anciano , Anciano de 80 o más Años , Acuaporinas/genética , Línea Celular , Línea Celular Tumoral , Humanos , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Próstata/citología , ARN/aislamiento & purificación , ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Chemotherapy-induced alopecia (CIA) is the most visibly distressing side effect of commonly administered chemotherapeutic agents. Because psychological health has huge relevance to lifestyle, diet, and self-esteem, it is important for clinicians to fully appreciate the psychological burden that CIA can place on patients. Here, for the first time to our knowledge, we provide a comprehensive review encompassing the molecular characteristics of the human hair follicle (HF), how different anticancer agents damage the HF to cause CIA, and subsequent HF pathophysiology, and we assess known and emerging prevention modalities that have aimed to reduce or prevent CIA. We argue that, at present, scalp cooling is the only safe and U.S. Food and Drug Administration-cleared modality available, and we highlight the extensive available clinical and experimental (biological) evidence for its efficacy. The likelihood of a patient that uses scalp cooling during chemotherapy maintaining enough hair to not require a wig is approximately 50%. This is despite different types of chemotherapy regimens, patient-specific differences, and possible lack of staff experience in effectively delivering scalp cooling. The increased use of scalp cooling and an understanding of how to deliver it most effectively to patients has enormous potential to ease the psychological burden of CIA, until other, more efficacious, equally safe treatments become available. IMPLICATIONS FOR PRACTICE: Chemotherapy-induced alopecia (CIA) represents perhaps the most distressing side effect of chemotherapeutic agents and is of huge concern to the majority of patients. Scalp cooling is currently the only safe option to combat CIA. Clinical and biological evidence suggests improvements can be made, including efficacy in delivering adequately low temperature to the scalp and patient-specific cap design. The increased use of scalp cooling, an understanding of how to deliver it most effectively, and biological evidence-based approaches to improve its efficacy have enormous potential to ease the psychological burden of CIA, as this could lead to improvements in treatment and patient quality-of-life.