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Sparc and melanoma

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https://www.readbyqxmd.com/read/27586584/prognostic-significance-of-immunohistochemical-epithelial-mesenchymal-transition-markers-in-skin-melanoma-patients
#1
Malgorzata Pieniazek, Piotr Donizy, Agnieszka Halon, Marek Leskiewicz, Rafal Matkowski
AIM: To investigate secreted protein acidic and rich in cystein (SPARC) and neural cadherin (NCAD), which are associated with epithelial-mesenchymal transition in primary skin melanoma and nodal metastases and their prognostic impact in melanoma patients. METHODS: Expression of proteins was assessed by immunochemistry in archival paraffin samples from 103 primary melanoma tumors and 16 nodal metastases. RESULTS: Increased expression of SPARC and NCAD in primary skin melanoma was associated with decreased overall survival, adverse clinicopathological features and particularly with microsatellitosis (SPARC) and ulceration (NCAD)...
September 2016: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27105498/stabilin-1-is-expressed-in-human-breast-cancer-and-supports-tumor-growth-in-mammary-adenocarcinoma-mouse-model
#2
Vladimir Riabov, Shuiping Yin, Bin Song, Aida Avdic, Kai Schledzewski, Ilja Ovsiy, Alexei Gratchev, Maria Llopis Verdiell, Carsten Sticht, Christina Schmuttermaier, Hiltrud Schönhaber, Christel Weiss, Alan P Fields, Katja Simon-Keller, Frederick Pfister, Sebastian Berlit, Alexander Marx, Bernd Arnold, Sergij Goerdt, Julia Kzhyshkowska
Stabilin-1 is a multifunctional scavenger receptor expressed on alternatively-activated macrophages. Stabilin-1 mediates phagocytosis of "unwanted-self" components, intracellular sorting, and endocytic clearance of extracellular ligands including SPARC that modulates breast cancer growth. The expression of stabilin-1 was found on tumor-associated macrophages (TAM) in mouse and human cancers including melanoma, lymphoma, glioblastoma, and pancreatic insulinoma. Despite its tumor-promoting role in mouse models of melanoma and lymphoma the expression and functional role of stabilin-1 in breast cancer was unknown...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/26410620/a-randomized-controlled-phase-iii-trial-of-nab-paclitaxel-versus-dacarbazine-in-chemotherapy-na%C3%A3-ve-patients-with-metastatic-melanoma
#3
RANDOMIZED CONTROLLED TRIAL
E M Hersh, M Del Vecchio, M P Brown, R Kefford, C Loquai, A Testori, S Bhatia, R Gutzmer, R Conry, A Haydon, C Robert, S Ernst, J Homsi, J J Grob, K Kendra, S S Agarwala, M Li, A Clawson, C Brachmann, M Karnoub, I Elias, M F Renschler, A Hauschild
BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS)...
November 2015: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/26248315/sparc-controls-melanoma-cell-plasticity-through-rac1
#4
Edgardo Salvatierra, Mariano J Alvarez, Claudia C Leishman, Elvia Rivas Baquero, Viviana P Lutzky, H Eduardo Chuluyan, Osvaldo L Podhajcer
Cell transition to a more aggressive mesenchymal-like phenotype is a hallmark of cancer progression that involves different steps and requires tightly regulated cell plasticity. SPARC (Secreted Protein Acidic and Rich in Cysteine) is a matricellular protein that promotes this transition in various malignant cell types, including melanoma cells. We found that suppression of SPARC expression in human melanoma cells compromised cell migration, adhesion, cytoskeleton structure, and cell size. These changes involved the Akt/mTOR pathway...
2015: PloS One
https://www.readbyqxmd.com/read/25925867/tumour-derived-sparc-drives-vascular-permeability-and-extravasation-through-endothelial-vcam1-signalling-to-promote-metastasis
#5
Mélanie Tichet, Virginie Prod'Homme, Nina Fenouille, Damien Ambrosetti, Aude Mallavialle, Michael Cerezo, Mickaël Ohanna, Stéphane Audebert, Stéphane Rocchi, Damien Giacchero, Fériel Boukari, Maryline Allegra, Jean-Claude Chambard, Jean-Philippe Lacour, Jean-François Michiels, Jean-Paul Borg, Marcel Deckert, Sophie Tartare-Deckert
Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling...
2015: Nature Communications
https://www.readbyqxmd.com/read/25802234/scd5-induced-oleic-acid-production-reduces-melanoma-malignancy-by-intracellular-retention-of-sparc-and-cathepsin-b
#6
Maria Bellenghi, Rossella Puglisi, Francesca Pedini, Alessandra De Feo, Federica Felicetti, Lisabianca Bottero, Sabina Sangaletti, Maria Cristina Errico, Marina Petrini, Cinzia Gesumundo, Massimo Denaro, Nadia Felli, Luca Pasquini, Claudio Tripodo, Mario Paolo Colombo, Alessandra Carè, Gianfranco Mattia
A proper balance between saturated and unsaturated fatty acids (FAs) is required for maintaining cell homeostasis. The increased demand of FAs to assemble the plasma membranes of continuously dividing cancer cells might unbalance this ratio and critically affect tumour outgrowth. We unveiled the role of the stearoyl-CoA desaturase SCD5 in converting saturated FAs into mono-unsaturated FAs during melanoma progression. SCD5 is down-regulated in advanced melanoma and its restored expression significantly reduced melanoma malignancy, both in vitro and in vivo, through a mechanism governing the secretion of extracellular matrix proteins, such as secreted protein acidic and rich in cysteine (SPARC) and collagen IV and of their proteases, such as cathepsin B...
July 2015: Journal of Pathology
https://www.readbyqxmd.com/read/24993904/sparc-osteonectin-is-involved-in-metastatic-process-to-the-lung-during-melanoma-progression
#7
Gerardo Botti, Giosuè Scognamiglio, Laura Marra, Francesca Collina, Maurizio Di Bonito, Margherita Cerrone, Bruna Grilli, Annamaria Anniciello, Renato Franco, Franco Fulciniti, Paolo Antonio Ascierto, Monica Cantile
The existence of a "metastasis gene signature" that predisposes primary breast cancer cells to metastasize to the lungs has been recently highlighted by gene expression profiling studies. The combination of genes responsible for this process includes genes encoding several metalloproteinases as well as the gene encoding SPARC (secreted protein acidic and rich in cysteine)/osteonectin. SPARC is involved in normal tissue remodeling as it regulates the deposition of extracellular matrix, but also plays a role in neoplastic transformation...
September 2014: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/24947586/sparc-in-tumor-pathophysiology-and-as-a-potential-therapeutic-target
#8
REVIEW
Jianguo Feng, Liling Tang
Cell migration and metastasis greatly contribute to the progression of tumors. Secreted Protein and Rich in Cysteine (SPARC), as a multi-faceted protein, is highly expressed in highly metastatic tumors while low or undetectable in less metastatic types with aberrant promoter methylation. In highly metastatic tumors, such as glioblastomas, melanoma, breast cancer and prostate cancer, SPARC promotes bone metastasis and epithelial-mesenchymal transition (EMT). In contrast, this protein acts as an anti-tumor factor in anti-angiogenesis, pro-apoptosis, cell proliferation inhibition and cell cycle arrest in less metastatic tumors, such as neuroblastoma, ovarian cancer, pancreatic cancer, colorectal cancer and gastric cancer...
2014: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/24460977/fkbp51-increases-the-tumour-promoter-potential-of-tgf-beta
#9
Simona Romano, Anna D'Angelillo, Paolo D'Arrigo, Stefania Staibano, Adelaide Greco, Arturo Brunetti, Massimiliano Scalvenzi, Rita Bisogni, Iris Scala, Maria Fiammetta Romano
BACKGROUND: FKBP51 (FKBP5 Official Symbol) is a large molecular weight component of the family of FK506 binding proteins (FKBP). In recent years, research studies from our laboratory highlighted functions for FKBP51 in the control of apoptosis and melanoma progression. FKBP51 expression correlated with the invasiveness and aggressiveness of melanoma. Since a role for TGF-β in the enhanced tumorigenic potential of melanoma cells is widely described, we hypothesized a cooperative effect between FKBP51 and TGF-β in melanoma progression...
2014: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/23974224/desmoplastic-melanoma-expression-of-epithelial-mesenchymal-transition-related-proteins
#10
Maria Concepción Garrido, Luis Requena, Heinz Kutzner, Pablo Ortiz, Beatriz Pérez-Gómez, José-Luis Rodriguez-Peralto
Desmoplastic melanoma (DM) is a rare variant of melanoma. Most frequently, it seems as clinically ambiguous and histologically characterized by a poorly demarcated neoplasm composed of a proliferation of spindle melanocytes dispersed in a prominent collagenous stroma. It often represents a diagnostic challenge, delaying its detection. We analyzed the expression profile of 29 (28 "pure" and 1 "combined") DM. These data were compared with a series of 62 primary vertical growth phase nondesmoplastic melanomas (NDMs) using a set of proteins including melanocytic markers (S-100 protein and melan-A) and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, SPARC, WT1, and PKCα)...
March 2014: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/23904381/silencing-endothelin-3-expression-attenuates-the-malignant-behaviors-of-human-melanoma-cells-by-regulating-sparc-levels
#11
Xiang-jie An, Yan-qiu Li, Xiao-ying Qu, Jing Zhang, Ling-yun Zhang, Ming Wang, Li Zhu, Si-yuan Chen, Hong-xiang Chen, Ya-ting Tu, Yu-wen Zhou, Chang-zheng Huang
Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined...
August 2013: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/23741061/metformin-blocks-melanoma-invasion-and-metastasis-development-in-ampk-p53-dependent-manner
#12
Michaël Cerezo, Mélanie Tichet, Patricia Abbe, Mickaël Ohanna, Abdelali Lehraiki, Florian Rouaud, Maryline Allegra, Damien Giacchero, Philippe Bahadoran, Corine Bertolotto, Sophie Tartare-Deckert, Robert Ballotti, Stéphane Rocchi
Metformin was reported to inhibit the proliferation of many cancer cells, including melanoma cells. In this report, we investigated the effect of metformin on melanoma invasion and metastasis development. Using different in vitro approaches, we found that metformin inhibits cell invasion without affecting cell migration and independently of antiproliferation action. This inhibition is correlated with modulation of expression of proteins involved in epithelial-mesenchymal transition such as Slug, Snail, SPARC, fibronectin, and N-cadherin and with inhibition of MMP-2 and MMP-9 activation...
August 2013: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/23690170/stromal-expression-of-sparc-in-pancreatic-adenocarcinoma
#13
REVIEW
Cindy Neuzillet, Annemilaï Tijeras-Raballand, Jérôme Cros, Sandrine Faivre, Pascal Hammel, Eric Raymond
Pancreatic ductal adenocarcinoma (PDAC) stands as the poorest prognostic tumor of the digestive tract, with a 5-year survival rate of less than 5%. Therapeutic options for unresectable PDAC are extremely limited and there is a pressing need for expanded therapeutic approaches to improve current options available with gemcitabine-based regimens. With PDAC displaying one of the most prominent desmoplastic stromal reactions of all carcinomas, recent research has focused on the microenvironment surrounding PDAC cells...
December 2013: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/23604101/therapeutic-improvement-of-a-stroma-targeted-crad-by-incorporating-motives-responsive-to-the-melanoma-microenvironment
#14
Diego L Viale, Eduardo G Cafferata, David Gould, Cecilia Rotondaro, Yuti Chernajovsky, David T Curiel, Osvaldo L Podhajcer, M Veronica Lopez
We have previously designed a conditionally replicative oncolytic adenovirus (CRAd) named Ad-F512 that can target both the stromal and the malignant melanoma cell compartments. The replication capacity of this CRAd is driven by a 0.5-Kb SPARC promoter fragment (named F512). To improve CRAd's efficacy, we cloned into F512 motives responsive to hypoxia (hypoxia-responsive element (HRE)) and inflammation (nuclear factor kappa B) to obtain a chimeric promoter named κBF512HRE. Using luciferase as a reporter gene, we observed 10-15-fold increased activity under hypoxia and 10-80-fold induction upon tumor necrosis factor-α addition...
November 2013: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/23516489/the-expression-of-sparc-in-human-intracranial-aneurysms-and-its-relationship-with-mmp-2-9
#15
Bo Li, Feng Li, Lingyi Chi, Liangwen Zhang, Shugan Zhu
OBJECTIVE: SPARC is a key determinant of invasion and metastasis in some tumors, such as gliomas, melanomas and prostate tumors. SPARC can change the composition and structure of the matrix and promote angiogenesis; these effects are closely related to clinical stage and the prognosis of tumors such as meningiomas. However, little is known about the expression of SPARC in intracranial aneurysms. The goal of this study was to establish the role of SPARC in human intracranial aneurysms...
2013: PloS One
https://www.readbyqxmd.com/read/23379109/-nab-paclitaxel-clinical-value-of-an-innovative-taxane-containing-formulation
#16
REVIEW
Hans-Peter Lipp
Nanoparticle-albumin bound paclitaxel (nab-paclitaxel) represents an innovative taxane-containing formulation lacking any critical solvents with minimal risks for any hypersensitivity reactions as well as perspectives for dose escalation as a consequence. Preclinical data indicated an increase of drug accumulation in tumor tissues via nab-paclitaxel administration which appears to be related to direct interaction with albumin-binding proteins including stromal SPARC. Phase III study results revealed clinically relevant advantages regarding efficacy and tolerability associated with nab-paclitaxel compared to conventional docetaxel and paclitaxel in patients with metastatic breast cancer...
January 2013: Medizinische Monatsschrift Für Pharmazeuten
https://www.readbyqxmd.com/read/22911700/the-epithelial-mesenchymal-transition-emt-regulatory-factor-slug-snai2-is-a-downstream-target-of-sparc-and-akt-in-promoting-melanoma-cell-invasion
#17
Nina Fenouille, Mélanie Tichet, Maeva Dufies, Anaïs Pottier, Ariane Mogha, Julia K Soo, Stéphane Rocchi, Aude Mallavialle, Marie-Dominique Galibert, Amir Khammari, Jean-Philippe Lacour, Robert Ballotti, Marcel Deckert, Sophie Tartare-Deckert
During progression of melanoma, malignant melanocytes can be reprogrammed into mesenchymal-like cells through a process similar to epithelial-mesenchymal transition (EMT), which is associated with downregulation of the junctional protein E-cadherin and acquisition of a migratory phenotype. Recent evidence supports a role for SLUG, a transcriptional repressor of E-cadherin, as a melanocyte lineage transcription factor that predisposes to melanoma metastasis. However, the signals responsible for SLUG expression in melanoma are unclear and its role in the invasive phenotype is not fully elucidated...
2012: PloS One
https://www.readbyqxmd.com/read/22760065/upregulation-of-alpha-and-beta-integrin-subunits-in-metastatic-macrophage-melanoma-fusion-hybrids
#18
Ashok K Chakraborty, Yoko Funasaka, Masamitsu Ichihashi, John M Pawelek
Fusion of cancer cells with migratory bone-marrow-derived cells such as macrophages can produce cancer cells with increased metastatic potential. To study this, we fused mouse macrophages with weakly metastatic mouse melanoma cells and generated a panel of hybrid clones. About half of these showed increased metastatic potential in mice. These hybrids expressed traits and molecules that were known indicators of tumor progression in melanoma (chemotaxis toward fibronectin, melanogenesis, autophagy, cMet, MCR1, SPARC, cell surface LAMP-1, GnT-V and β1,6-branched oligosaccharides)...
December 2009: Melanoma Research
https://www.readbyqxmd.com/read/21850018/sparc-promotes-cathepsin-b-mediated-melanoma-invasiveness-through-a-collagen-i-%C3%AE-2%C3%AE-1-integrin-axis
#19
María R Girotti, Marisol Fernández, Juan A López, Emilio Camafeita, Elmer A Fernández, Juan P Albar, Lorena G Benedetti, María P Valacco, Rolf A Brekken, Osvaldo L Podhajcer, Andrea S Llera
In melanoma, the extracellular protein SPARC (secreted protein acidic and rich in cysteine) is related to tumor progression. Some of the evidence that links SPARC to melanoma progression indicates that SPARC may be involved in the acquisition of mesenchymal traits that favor metastatic dissemination. However, no molecular pathways that link extracellular SPARC to a mesenchymal phenotype have been described. In this study, global protein expression analysis of the melanoma secretome following enforced downregulation of SPARC expression led us to elucidate a new molecular mechanism by which SPARC promotes cathepsin B-mediated melanoma invasiveness using collagen I and α2β1 integrins as mediators...
December 2011: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/21815687/proteomic-profiling-of-human-melanoma-metastatic-cell-line-secretomes
#20
Micaela Rocco, Livia Malorni, Rosaria Cozzolino, Giuseppe Palmieri, Carla Rozzo, Antonella Manca, Augusto Parente, Angela Chambery
During the last few years, the incidence and mortality of human melanoma have rapidly increased. Metastatic spread of malignant melanoma is often associated with cancer progression with poor prognosis and survival. These processes are controlled by dynamic interactions between tumor melanocytes and neighboring stromal cells, whose deregulation leads to the acquisition of cell proliferation capabilities and invasiveness. It is increasingly clear that a key role in carcinogenesis is played by secreted molecules either by tumor and surrounding stromal cells...
October 7, 2011: Journal of Proteome Research
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