Gemcitabine remains a cornerstone in chemotherapy of pancreatic ductal adenocarcinoma (PDAC) despite suboptimal clinical effects that are partly due to the development chemoresistance. Pancreatic stellate cells (PSCs) tumor stroma known interact with cancer (PCCs) and influence progression PDAC through complex network signaling molecules involve extracellular matrix (ECM) proteins. To understand tumor-stroma interactions regulating chemosensitivity, role PSC-secreted fibronectin (FN)...

Pancreatic ductal adenocarcinoma is characterized by a prominent fibroinflammatory stroma with both tumor-promoting and tumor-suppressive functions. The pancreatic stellate cell (PSC) the major cellular stromal component main producer of extracellular matrix proteins, including collagens, which are degraded metalloproteinases (MMPs). PSCs interact cancer cells through various factors, transforming growth factor (TGF)β interleukin (IL)-1α. role TGFβ in dual nature tumor stroma, i.e.,...

Profound resistance to chemotherapy remains a major challenge in achieving better clinical outcomes for patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies indicate that gemcitabine (GEM) is promoted both by stellate cells (PSCs) and through increased glycolysis. However, it unknown whether PSCs affect GEM sensitivity via glycolytic regulation.Human cancer cell (PCC) lines (BxPC-3, Capan-2, HPAF-II, Mia PaCa-2, Panc-1, SW-1990) were exposed three different PSC-conditioned...

Neurotensin has been found to promote colon carcinogenesis in rats and mice, proliferation of human carcinoma cell lines, but the mechanisms involved are not clear. We have examined signalling pathways activated by neurotensin colorectal pancreatic cells. Colon lines HCT116 HT29 adenocarcinoma line Panc-1 were cultured stimulated with or epidermal growth factor (EGF). DNA synthesis was determined incorporation radiolabelled thymidine into DNA. Levels phosphorylation proteins assessed Western...

Oral squamous cell carcinoma is an aggressive neoplasm with serious morbidity and mortality, which typically spreads through local invasive growth. Lysophosphatidic acid (LPA) involved in a number of biological processes, may have role cancer migration invasiveness. LPA present most tissues can activate cells six different receptors (LPAR1-6). Although predominantly promigratory, some the antimigratory effects certain cells. The signalling mechanisms are not fully understood, oral specific...

Activated pancreatic stellate cells (PSCs) play a central role in the tumor stroma of ductal adenocarcinoma (PDAC). Given limited availability patient-derived PSCs from PDAC, immortalized PSC cell lines murine and human origin have been established; however, it is not elucidated whether differences species, organ disease status, donor age, immortalization alter phenotype behavior compared to that primary cultures. Therefore, panel commonly used cultures was examined for important...

Abstract Prostaglandins (PGs) such as PGE 2 enhance proliferation in many cells, apparently through several distinct mechanisms, including transactivation of the epidermal growth factor (EGF) receptor (EGFR) well EGFR‐independent pathways. In this study we found that primary cultures rat hepatocytes did not induce phosphorylation EGFR, and EGFR tyrosine kinase blockers gefitinib AG1478 affect ‐stimulated ERK1/2. contrast, elicited inhibitor‐sensitive ERK MH 1 C hepatoma cells. These findings...

Gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC) is attributed to cancer cell-intrinsic drug processing and the impact of tumor microenvironment, especially stellate cells (PSCs). This study uses human PDAC-derived paired primary (PCCs) PSCs from four different tumors, PDAC cell lines BxPC-3, Mia PaCa-2, Panc-1, assess fate gemcitabine by measuring its cellular uptake, cytotoxicity, LC-MS/MS-based metabolite analysis. Expression analysis siRNA-mediated knockdown key...

It is important to understand the mechanisms by which cells integrate signals from different receptors. Several lines of evidence implicate epidermal growth factor (EGF) receptor (EGFR) in pathophysiology hepatocarcinomas. Data also suggest a role prostaglandins some these tumours, through their receptors G protein-coupled (GPCR) family. In this study we have investigated interaction between signalling prostaglandin and EGFR hepatocarcinoma cells. The rat cell line MH1C1 normal hepatocytes...

Several studies have described an increased cyclooxygenase-2 (COX-2) expression in pancreatic cancer, but the role of COX-2 tumour development and progression is not clear. The aim present study was to examine cancer cells stromal specimens, explore PGE2 stellate cell proliferation collagen synthesis.Immunohistochemistry immunofluorescence performed on slides from whole sections tissue blocks using antibodies against α-smooth muscle actin (αSMA). Pancreatic (PSC) were isolated surgically...

The most abundant cells in the extensive desmoplastic stroma of pancreatic adenocarcinomas are stellate cells, which interact with carcinoma and strongly influence progression cancer. Tumor interactions induced by IL-1α/IL-1R1 signaling have been shown to be involved cancer cell migration. TGFβ its receptors overexpressed adenocarcinomas. We aimed at exploring IL-1α cross-talk regulating adenocarcinoma Human were isolated from surgically resected cultured presence or lines. effects blocked...

J Oral Pathol Med (2012) 41 : 547–558 Background: Cell migration is a necessary part of malignant invasiveness. squamous cell carcinomas (OSCC) have great tendency for local invasive growth. We investigated signalling pathways involved in induced by epidermal growth factor (EGF) and hepatocyte (HGF) OSCC cells examined the effects various experimental clinically approved anti‐tumour signal inhibitors on migratory activity. Methods: Migration was studied three human lines, using scratch wound...

Guanylyl cyclase-B (GC-B; natriuretic peptide receptor-B, NPR-B) stimulation by C-type (CNP) increases cGMP and causes a lusitropic negative inotropic response in adult myocardium. These effects are not mimicked NPR-A (GC-A) brain (BNP), despite similar increase. More refined methods needed to better understand the mechanisms of differential signalling compartmentation. The aim this work was measure near proteins involved regulating contractility compartmentation cardiomyocytes.

Lysophosphatidic acid (LPA) is a small glycerophospholipid ubiquitously present in tissues and plasma. It acts through receptors belonging to the G-protein-coupled receptor (GPCR) family, involved several biological processes, strongly implicated different cancers. In this paper, we have investigated effects of LPA on DNA synthesis migration panel pancreatic colon cancer cells, with particular focus involvement epidermal growth factor (EGF) (EGFR) LPA-induced signaling. stimulated and/or all...

The pancreatic stellate cell (PSC) is the principal type of desmoplastic stroma ductal adenocarcinoma (PDAC). PSCs interact with cancer cells and influence progression disease through a complex network signaling molecules including hepatocyte growth factor (HGF). Functional heterogeneity within tumor might conceivably progression. We investigated PSC populations isolated from different human PDACs examined effects PSC-conditioned medium on BxPC-3 AsPC-1 cells. exhibited wide range variation...

Abstract The receptor tyrosine kinases EGFR and Met induce phosphorylation of the docking protein Gab1, there is evidence that Gab1 may have a role in signaling from these receptors. Studying hepatocytes, we previously found although mechanistically interacted different ways with Met, it was involved mitogenic induced by both EGF HGF. It has been reported EGFR, required particularly at low dose EGF. Whether this also applies to HGF/Met not investigated. We studied activation Akt ERK pathways...

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis, and its treatment remains a challenge. As the existing in vitro experimental models offer only limited resemblance to human PDAC, there strong need for additional research tools better understand PDAC tumor biology, particularly impact of stroma. Here, we report first time establishment characterization PDAC-derived paired primary monolayer cultures (epithelial) cancer cells (PCCs) mesenchymal stellate...

Hepatocytes are responsive to mitogenic effects of several ligands acting via EGFR. Studying primary cultures rat hepatocytes, we found that, as compared EGF, HB-EGF had a markedly higher affinity the EGFR, while AR and TGFα lower affinity. was also more potent other growth factors regarding phosphorylation Shc, ERK1/2 Akt. All induced ErbB2, indicating receptor heterodimerization. TGFα, despite having much affinity, about equally efficacious stimulator DNA synthesis. In contrast, EGF...

Previous studies in rat hepatocytes have shown that the MEK/ERK, PI3K/Akt and p38 pathways are all involved activation of DNA synthesis by EGF sustained MEK/ERK is required. Here, we show although HGF stimulated activated signaling same manner as EGF, contribution to induction differed. While HGF-induced was dependent on with no significant from PI3K/Akt, suppressed synthesis. The inhibitor SB203580 increased enhanced phosphorylation ERK. In contrast, decreased EGF-induced ERK...

<p class="first" dir="auto" id="d3301962e120">Natriuretic peptides (NPs) are cardiac hormones that play a significant role in functioning of the heart and promising for treatment failure. NPs increase cGMP levels by activating two NP receptors, NPR-A (ANP BNP) NPR-B (CNP). However, influence these receptors on contractility various intracellular targets is not same. Our aim to study if activity NPRs differentially regulated interacting proteins, cytohesins. id="d3301962e122">By Western...