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Sparc and melanoma

Shakuntala H Mauzo, Denái R Milton, Victor G Prieto, Carlos A Torres-Cabala, Wei-Lien Wang, Nitin Chakravarti, Priyadharsini Nagarajan, Michael T Tetzlaff, Jonathan L Curry, Doina Ivan, Robert E Brown, Phyu P Aung
BACKGROUND: Serum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein, which regulates cell proliferation and facilitates intracellular transport of albumin bound particles including chemotherapeutic agents such as Nab-paclitaxel/ABI-007. Therefore the presence of SPARC may achieve higher intra-tumoral drug concentration with lower dosage and thus reduce systemic side-effects. Several trials of ABI-007, in melanoma, show promising clinical activity. DESIGN: Fifty-four cases of dermal based neoplasms were retrieved including 24 angiosarcomas (AS), 10 hemangiomas, 9 nodular melanomas, 4 Kaposi sarcomas (KS), 3 leiomyosarcomas (LMS), 3 atypical fibroxanthomas (AFX) and 1 spindle cell squamous cell carcinoma (SSCC)...
March 15, 2018: Annals of Diagnostic Pathology
Piotr Donizy, Maciej Kaczorowski, Przemyslaw Biecek, Agnieszka Halon, Rafal Matkowski
Nuclear pseudoinclusions (NPIs) are classically found in papillary thyroid carcinoma and meningioma. Although NPIs have been described in melanocytic lesions, there is no systematic analysis of potential relationship between NPIs and other clinicopathological characteristics of melanoma. We examined the presence of NPIs in H&E-stained tissue sections form 96 melanomas and analyzed statistical associations with important clinicopathological parameters and tissue immunoreactivity for selected proteins involved in epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and mobility (ALCAM, ADAM-10), regulation of mitosis (PLK1), cell survival (FOXP1) and functioning of Golgi apparatus (GOLPH3, GP73)...
February 2018: Pathology International
Salma Kaochar, Jianrong Dong, Marie Torres, Kimal Rajapakshe, Fotis Nikolos, Christel M Davis, Erik A Ehli, Cristian Coarfa, Nicholas Mitsiades, Vasiliki Poulaki
Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic chemotherapies, thus creating an urgent need for novel therapeutics. In this study, we investigated the sensitivity of UM cells to ICG-001, a small molecule reported to suppress the Wnt/β-catenin-mediated transcriptional program. Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on cellular proliferation, migration, and gene expression. In vivo efficacy of ICG-001 was evaluated in a UM xenograft model...
January 1, 2018: Investigative Ophthalmology & Visual Science
Piotr Donizy, Przemyslaw Biecek, Agnieszka Halon, Adam Maciejczyk, Rafal Matkowski
BACKGROUND: The nucleolus is an organelle that is an ultrastructural element of the cell nucleus observed in H&E staining as a roundish body stained with eosin due to its high protein content. Changes in the nucleoli cytomorphology were one of the first histopathological characteristics of malignant tumors. The aim of this study was to assess the relationship between the cytomorphological characteristics of nucleoli and detailed clinicopathological parameters of melanoma patients...
December 29, 2017: Diagnostic Pathology
Joonyoung Park, Bo Sun, Yoon Yeo
Nanoparticles are used to deliver anticancer drugs to solid tumors. However, clinical development of nanoparticles is challenging because of their limitations in physicochemical properties, such as low drug loading efficiency and poor circulation stability. Low drug loading not only causes technical difficulty in administration but also increases the amount of co-delivered carrier materials, imposing biological burdens to patients. Poor circulation stability causes loss of pharmacokinetics benefits of nanoparticles...
October 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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