Search results for "Amphiregulin"

Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG) and activate the epidermal growth factor pathway in the bone microenvironment l…

2019

Background Multiple myeloma (MM) is a clonal plasma cell malignancy associated with osteolytic bone disease. Recently, the role of MM-derived exosomes in the osteoclastogenesis has been demonstrated although the underlying mechanism is still unknown. Since exosomes-derived epidermal growth factor receptor ligands (EGFR) are involved in tumor-associated osteolysis, we hypothesize that the EGFR ligand amphiregulin (AREG) can be delivered by MM-derived exosomes and participate in MM-induced osteoclastogenesis. Methods Exosomes were isolated from the conditioned medium of MM1.S cell line and from bone marrow (BM) plasma samples of MM patients. The murine cell line RAW264.7 and primary human CD1…

Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway

2017

AbstractNon-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung. Its levels in plasma of NSCLC patients correlate with poor prognosis and AREG was recently …

Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor

2016

Abstract Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. Recent evidence indicates that altered crosstalk between CML and mesenchymal stromal cells may affect leukaemia survival; moreover, vesicles released by both tumour and non‐tumour cells into the microenvironment provide a suitable niche for cancer cell growth and survival. We previously demonstrated that leukaemic and stromal cells establish an exosome‐mediated bidirectional crosstalk leading to the production of IL8 in stromal cells, thus sustaining the survival of CML cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone marrow primary stromal cells; gene expression and protei…

PO-146 Multiple myeloma-derived exosomes carry amphiregulin and are responsible for the uncoupled bone remodelling

2018

Introduction Multiple myeloma (MM) is a hematologic malignancy associated with osteolytic bone disease caused by the perturbation of the functional balance between bone resorption and bone formation. Exosomes, nanosize lipoproteic structures, have been recently recognised as a new mechanism of cell to cell communication during tumour growth and progression. We have previously shown that MM-exosomes are involved in osteolytic lesions but the underlying mechanism is still understood. We hypothesise that the epidermal growth factor receptor ligand Amphiregulin (AREG) can be delivered by multiple myeloma-derived exosomes and participate in modulating the response of the bone microenvironment to…

The Exosomes-derived EGFR Ligand Amphiregulin (AREG) is a new key player in Multiple Myeloma Bone Destruction

Il Mieloma Multiplo (MM) è caratterizzato dalla presenza di aree osteolitiche dovute alla presenza di plasmacellule (PC) neoplastiche che causano l'interruzione della normale omeostasi ossea, promuovendo l'attività degli osteoclasti (OC) ed inibendo la funzione degli (OB). Al momento, uno dei campi di ricerca nella fisiopatologia del MM è proprio lo studio dei meccanismi che regolano l’attività degli OC e degli OB così come l’identificazione di target terapeutici per la prevenzione ed il trattamento delle lesioni osteolitiche. Negli ultimi anni è emerso che le vescicole extracellulari (EV), ed in particolare gli esosomi, giocano un ruolo fondamentale nel mediare il cross-talk tra le cellule…

Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis

2015

AbstractAmphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-α converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also ass…

Aromatase and amphiregulin are correspondingly expressed in human liver cancer cells

2009

Human hepatocellular carcinoma (HCC) is associated with high mortality rates, being the third most common cause of cancer death worldwide. Although estrogens have been implicated in HCC, their potential role in development and/or progression of this malignancy remains unclear. In this study we investigated mRNA and protein expression of aromatase (Aro) and amphiregulin (AREG) in relation to estrogen receptors (ERs), in HepG2, Huh7, and HA22T human malignant liver cell lines, using RT-PCR and Western blot analyses. Aro expression was significantly higher (approximately 13-fold, P= 0.003) in HepG2 cells than in Huh7 cells, while no Aro expression could be detected in HA22T cells. Interestingl…