Search results for "Cellular protein"
showing 9 items of 19 documents
Prognostic relevance of CCN3 in Ewing sarcoma
2009
Ewing sarcoma is a highly aggressive malignant bone tumor occurring preferentially in children and young adults. At present, only clinical features, such as patient age, presence of clinically evident metastases at diagnosis, and poor response to neoadjuvant chemotherapy, are widely accepted as prognostic indicators in Ewing sarcoma. In this study, we assessed the prognostic value of CCN3 (Nov), a matricellular protein that play crucial roles in bone formation. Polyclonal antibodies directed against each of the different CCN3 modules were used to identify variant CCN3 proteins in tumors and to draw potential relationships between the expression of these variants and the outcome of patients …
Design and physicochemical characterization of poly(amidoamine) nanoparticles and the toxicological evaluation in human endothelial cells: applicatio…
2013
In this study, we investigated nanoparticles formulated by self-assembly of a biodegradable poly(amidoamine) (PAA) and a fluorescently labeled peptide, in their capacity to internalize in endothelial cells and deliver the peptide, with possible applications for brain drug delivery. The nanoparticles were characterized in terms of size, surface charge, and loading efficiency, and were applied on human cerebral microvascular endothelial cells (hCMEC/D3) and human umbilical vein endothelial cells (Huvec) cells. Cell-internalization and cytotoxicity experiments showed that the PAA-based nanocomplexes were essentially nontoxic, and the peptide was successfully internalized into cells. The result…
Defective stromal remodeling and neutrophil extracellular traps in lymphoid tissues favor the transition from autoimmunity to lymphoma
2013
Abstract Altered expression of matricellular proteins can become pathogenic in the presence of persistent perturbations in tissue homeostasis. Here, we show that autoimmunity associated with Fas mutation was exacerbated and transitioned to lymphomagenesis in the absence of SPARC (secreted protein acidic rich in cysteine). The absence of SPARC resulted in defective collagen assembly, with uneven compartmentalization of lymphoid and myeloid populations within secondary lymphoid organs (SLO), and faulty delivery of inhibitory signals from the extracellular matrix. These conditions promoted aberrant interactions between neutrophil extracellular traps and CD5+ B cells, which underwent malignant …
SPARC oppositely regulates inflammation and fibrosis in bleomycin-induced lung damage.
2011
Fibrosis results from inflammatory tissue damage and impaired regeneration. In the context of bleomycin-induced pulmonary fibrosis, we demonstrated that the matricellular protein termed secreted protein acidic and rich in cysteine (SPARC) distinctly regulates inflammation and collagen deposition, depending on its cellular origin. Reciprocal Sparc(-/-) and wild-type (WT) bone marrow chimeras revealed that SPARC expression in host fibroblasts is required and sufficient to induce collagen fibrosis in a proper inflammatory environment. Accordingly, Sparc(-/-) >WT chimeras showed exacerbated inflammation and fibrosis due to the inability of Sparc(-/-) macrophages to down-regulate tumor necrosis …
Proteomic identification of the heterogeneous nuclear ribonucleoprotein K as irradiation responsive protein related to migration
2014
Abstract Irradiation resistance is a major obstacle of head and neck squamous cell carcinoma (HNSCC) therapy, limiting treatment success and patient survival. The aim of our experiments was to identify irradiation-regulated proteins as potential drug targets. Two established HNSCC cell lines (HNSCCUM-01T and HNSCCUM-02T) were treated with a single 8 Gy (Gray) fraction of irradiation. Changes in cellular protein expression were studied after 24 h by means of 2D-electrophoresis and MALDI–TOF-mass spectrometry. Ninety-four differentially expressed proteins were identified. The expression levels of four proteins were regulated similarly in both cell lines after irradiation treatment, i.e., GRP7…
Osteopontin shapes immunosuppression in the metastatic niche.
2014
Abstract The matricellular protein osteopontin (OPN, Spp-1) is widely associated with cancer aggressiveness when produced by tumor cells, but its impact is uncertain when produced by leukocytes in the context of the tumor stroma. In a broad study using Spp1−/− mice along with gene silencing in tumor cells, we obtained evidence of distinct and common activities of OPN when produced by tumor or host cells in a spontaneously metastatic model of breast cancer. Different cellular localization of OPN is associated with its distinct activities, being mainly secreted in tumor cells while intracellular in myeloid cells. OPN produced by tumor cells supported their survival in the blood stream, wherea…
Stromal niche communalities underscore the contribution of the matricellular protein SPARC to B-cell development and lymphoid malignancies
2014
Neoplastic B-cell clones commonly arise within secondary lymphoid organs (SLO). However, during disease progression, lymphomatous cells may also colonize the bone marrow (BM), where they localize within specialized stromal niches, namely the osteoblastic and the vascular niche, according to their germinal center-or extra-follicular-derivation, respectively. We hypothesized the existence of common stromal motifs in BM and SLO B-cell lymphoid niches involved in licensing normal B-cell development as well as in fostering transformed B lymphoid cells. Thus, we tested the expression of prototypical mesenchymal stromal cell (MSC) markers and regulatory matricellular proteins in human BM and SLO u…
Intra-tumor heterogeneity of Diffuse Large B-cell Lymphoma involves the induction of diversified stroma-tumor interfaces
2020
ABSTRACTIntra-tumor heterogeneity in lymphoid malignancies is articulated around several fundamentals, encompassing selection of genetic subclonal events and epigenetic regulation of transcriptional programs. Clonally-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-intrinsic mesenchymal determinants impact on the diversification of aggressive lymphomas is still unknown. In this study we adopted the established A20 line-based model of Diffuse Large B-cell Lymphoma (DLBCL), to investigate the intra-tumor heterogeneity associated with the infiltration of different tissue microenvironm…
Prognostic Relevance of CCN3 in Bone Sarcomas
2010
Osteosarcomas and Ewing’s sarcoma (EWS) are aggressive malignant bone tumors. In both cases, prognostic markers are lacking. Presently, only clinical features are widely accepted as prognostic indicators. In this study we assessed the prognostic value of CCN3 (Nov), a matricellular protein that belong to the CCN family of regulatory proteins, whose members were shown to play crucial roles in bone formation. In osteosarcomas, CCN3 expression levels represent a useful tool to early identification of patients with different prognosis. In both osteosarcomas and Ewing’s sarcomas, the expression of a full length CCN3 protein was associated to a worse prognostic and a higher risk to developing met…