target receptors androgen therapy has emerged as an effective tool for managing prostate cancer (PCa). However, the frequent occurrence of therapy resistance is a major challenge in the clinical management of the patient, as well as the molecular mechanisms behind resistance therapy is not yet fully understood.
In this study, we aimed to identify new targets for intervention with therapy resistance using gene expression analysis of PCa spheroids co-cultures in which the cells of PCa were grown in the presence of fibroblasts associated cancer (CAFS) and which had previously been shown to be reliable models for change antiandrogen resistance.Gene expression of co-culture spheroids (LNCaP and featured DuCaP together with the CAFS) identified by Illumina microarray profiles.
Real-time PCR, Western blotting, immunohistochemistry and cell viability tests in 2D and 3D cultures performed to validate the selected target expression in vitro and in vivo. cytokine profiles was conducted to analyze the CAF-conditioned medium.Gene co-culture expression analysis spheroids revealed that CAFS trigger a significant upregulation of cholesterol and steroid biosynthesis pathway in PCa cells. Cytokine profiling reveal a high number of pro-inflammatory factors, pro-migratory and pro-angiogenic in the supernatant CAF.
In particular, two genes, 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (HMGCS2) and aldo-keto reductase family 1 member C3 (AKR1C3), was significantly upregulated in PCa cells in co-culture with CAFS. Both enzymes also increased significantly in human PCa compared with benign tissue with AKR1C3 expression even associated with Gleason score and metastatic status. Inhibiting HMGCS2 and AKR1C3 resulted in a significant growth retardation of spheroids co-culture as well as a variety of castration and enzalutamide resistant cell lines in 2D and 3D cultures, underlining their alleged role in PCa.
Importantly, dual targeting cholesterol and steroid biosynthesis with simvastatin, commonly prescribed cholesterol synthesis inhibitors, and inhibitors to have the strongest growth inhibitory AKR1C3 effect.From our results we conclude that the CAFS induces upregulation of cholesterol and steroid biosynthesis in PCa cells, driving them to AR targeted therapy resistance. Hinder both paths with AKR1C3 inhibitor simvastatin and therefore may be a promising approach to overcome resistance to targeted therapies AR in PCa. Video abstract.
Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis.
Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an immunoregulatory Factor Mediates Airway Remodeling and Possible Pharmacological Target.
Asthma is a chronic disease of the respiratory system and heterogeneous, one of the most common lung diseases worldwide. The underlying pathology, the chronic inflammatory process and airway remodeling (AR), mediated by cells and cytokines.
Particularly interesting in this field is the platelet-derived growth factor (PDGF), one of the members of the family of human growth factors. In this article, the authors analyze the available data on the role of PDGF in asthma in experimental models and human studies. PDGF is expressed in the airway by a variety of cells contribute to the pathogenesis of asthma-mast cells, eosinophils and airway epithelial cells.
Description: A sandwich quantitative ELISA assay kit for detection of Chicken Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Equine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Equine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Human Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Human Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rabbit Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rabbit Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Sheep Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Sheep Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Monkey Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Monkey Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Guinea pig Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Guinea pig Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
The study confirms the thesis that this factor is also secreted by these cells in the course of asthma. The main effect of PDGF in the bronchus is the proliferation of airway smooth muscle cells (ASM) ASM to epithelial cell migration and enhanced collagen synthesis by pulmonary fibroblasts. AR importance in asthma is a well recognized and new therapies should also aim to manage it, perhaps targeting PDGFRs.
