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fibroblast cancer cell secretomes

Aihua Hou, Kai Pong Law, Min Qi Tin, Yoon Pin Lim, Louis Tong
Pterygium is a triangular shaped ocular fibrous surface lesion growing from conjunctiva towards central cornea, causing ocular irritation, astigmatism, and visual disturbance. The condition is characterized by epithelial proliferation, fibrovascular growth, chronic inflammation, and prominent extracellular matrix remodeling. Studies have suggested that aberrant extracellular proteins secreted by fibroblasts lead to abnormal matrix production and tissue invasion contributing to the development of the disease...
October 7, 2016: Experimental Eye Research
David W Greening, Hong Ji, Maoshan Chen, Bruce W S Robinson, Ian M Dick, Jenette Creaney, Richard J Simpson
Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation...
2016: Scientific Reports
Shashi K Gopal, David W Greening, Hong-Jian Zhu, Richard J Simpson, Rommel A Mathias
Epithelial-mesenchymal transition (EMT) enhances the migration and invasion of cancer cells, and is regulated by various molecular mechanisms including extracellular matrix metalloproteinase (MMP) activity. Previously, we reported transformation of epithelial Madin-Darby canine kidney (MDCK) cells with oncogenic H-Ras (21D1 cells) induces EMT, and significantly elevates MMP1 expression. To explore the biological significance, in this study we characterized 21D1 cells with knocked-down MMP1 expression (21D1(-MMP1))...
2016: Scientific Reports
S S Prime, N Cirillo, Y Hassona, D W Lambert, I C Paterson, M Mellone, G J Thomas, E N L James, E K Parkinson
There is now compelling evidence that the tumour stroma plays an important role in the pathogenesis of cancers of epithelial origin. The pre-eminent cell type of the stroma is carcinoma-associated fibroblasts. These cells demonstrate remarkable heterogeneity with activation and senescence being common stress responses. In this review, we summarise the part that these cells play in cancer, particularly oral cancer, and present evidence to show that activation and senescence reflect a unified programme of fibroblast differentiation...
May 30, 2016: Journal of Oral Pathology & Medicine
Siham Moatassim-Billah, Camille Duluc, Rémi Samain, Christine Jean, Aurélie Perraud, Emilie Decaup, Stéphanie Cassant-Sourdy, Youssef Bakri, Janick Selves, Herbert Schmid, Yvan Martineau, Muriel Mathonnet, Stéphane Pyronnet, Corinne Bousquet
Pancreatic ductal adenocarcinoma (PDA) shows a rich stroma where cancer-associated fibroblasts (CAFs) represent the major cell type. CAFs are master secretors of proteins with pro-tumor features. CAF targeting remains a promising challenge for PDA, a devastating disease where treatments focusing on cancer cells have failed. We previously introduced a novel pharmacological CAF-targeting approach using the somatostatin analog SOM230 (pasireotide) that inhibits protein synthesis in CAFs, and subsequent chemoprotective features of CAF secretome...
May 12, 2016: Oncotarget
Robert Büttner, Alexander Berndt, Christina Valkova, Petra Richter, Alexander Korn, Christian Kosan, Claus Liebmann
INTRODUCTION: Receptors of the ErbB family belong to the key players in cancer development and are targets of several therapeutic approaches. Their functional dependency on the tumor microenvironment, especially on CAFs is albeit still poorly understood. Our objective was to investigate the impact of CAF secretome on ErbB receptor expression and signaling behavior in OSCC. METHODS: Stimulation of PE/CA-PJ15 OSCC cells with conditioned media of TGF-β1-activated fibroblasts was used as model system for CAF to cancer cell communication...
April 6, 2016: Journal of Receptor and Signal Transduction Research
Takayuki Ishige, Motoi Nishimura, Mamoru Satoh, Mai Fujimoto, Masaki Fukuyo, Toshihisa Semba, Sayaka Kado, Sachio Tsuchida, Setsu Sawai, Kazuyuki Matsushita, Akira Togawa, Hisahiro Matsubara, Atsushi Kaneda, Fumio Nomura
Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types...
2016: Scientific Reports
Ming Ding, Richard K Bruick, Yonghao Yu
The PI(3)K-Akt-mTORC1 pathway is a highly dynamic network that is balanced and stabilized by a number of feedback inhibition loops. Specifically, activation of mTORC1 has been shown to lead to the inhibition of its upstream growth factor signalling. Activation of the growth factor receptors is triggered by the binding of their cognate ligands in the extracellular space. However, whether secreted proteins contribute to the mTORC1-dependent feedback loops remains unclear. We found that cells with hyperactive mTORC1 secrete a protein that potently inhibits the function of IGF-1...
March 2016: Nature Cell Biology
Elizabete Bagordakis, Iris Sawazaki-Calone, Carolina Carneiro Soares Macedo, Carolina M Carnielli, Carine Ervolino de Oliveira, Priscila Campioni Rodrigues, Ana Lucia C A Rangel, Jean Nunes Dos Santos, Juha Risteli, Edgard Graner, Tuula Salo, Adriana Franco Paes Leme, Ricardo D Coletta
An important role has been attributed to cancer-associated fibroblasts (CAFs) in the tumorigenesis of oral squamous cell carcinoma (OSCC), the most common tumor of the oral cavity. Previous studies demonstrated that CAF-secreted molecules promote the proliferation and invasion of OSCC cells, inducing a more aggressive phenotype. In this study, we searched for differences in the secretome of CAFs and normal oral fibroblasts (NOF) using mass spectrometry-based proteomics and biological network analysis. Comparison of the secretome profiles revealed that upregulated proteins involved mainly in extracellular matrix organization and disassembly and collagen metabolism...
July 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
M M Koczorowska, S Tholen, F Bucher, L Lutz, J N Kizhakkedathu, O De Wever, U F Wellner, M L Biniossek, A Stahl, S Lassmann, O Schilling
Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome ("secretome"), including reduced levels of anti-angiogenic factors, elevated levels of transforming growth factor (TGF) β, and an impact on matrix processing enzymes...
January 2016: Molecular Oncology
Sun-Xia Chen, Xiao-En Xu, Xiao-Qing Wang, Shu-Jian Cui, Lei-Lei Xu, Ying-Hua Jiang, Yang Zhang, Hai-Bo Yan, Qian Zhang, Jie Qiao, Peng-Yuan Yang, Feng Liu
The tumor cell proliferation, migration and invasion were influenced by the interaction between the cancer cells and their microenvironment. In current study, we established two pairs of the primary fibroblast cultures from colorectal adenocarcinoma tissues and the normal counterparts and identified 227 proteins in the colonic fibroblast secretomes; half of these proteins were novel. The mass spectrometry data and analyzed results presented here provide novel insights into the molecular characteristics and modulatory role of colon cancer associated fibroblasts...
December 2014: Data in Brief
Camille Duluc, Siham Moatassim-Billah, Mounira Chalabi-Dchar, Aurélie Perraud, Rémi Samain, Florence Breibach, Marion Gayral, Pierre Cordelier, Marie-Bernadette Delisle, Marie-Pierre Bousquet-Dubouch, Richard Tomasini, Herbert Schmid, Muriel Mathonnet, Stéphane Pyronnet, Yvan Martineau, Corinne Bousquet
Pancreatic ductal adenocarcinoma (PDAC) is extremely stroma-rich. Cancer-associated fibroblasts (CAFs) secrete proteins that activate survival and promote chemoresistance of cancer cells. Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of α-SMA-positive CAFs, isolated from human PDAC resections. CAFs selectively express the sst1 somatostatin receptor...
June 2015: EMBO Molecular Medicine
Ridwana Chowdhury, Jason P Webber, Mark Gurney, Malcolm D Mason, Zsuzsanna Tabi, Aled Clayton
Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood. We investigated the role of nano-metre sized vesicles (exosomes), secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM-MSC), and the subsequent functional consequences of such changes...
January 20, 2015: Oncotarget
Mieke Van Bockstal, Kathleen Lambein, Mireille Van Gele, Elly De Vlieghere, Ridha Limame, Geert Braems, Rudy Van den Broecke, Veronique Cocquyt, Hannelore Denys, Marc Bracke, Louis Libbrecht, Olivier De Wever
Cancer progression is characterized by a complex reciprocity between neoplastic epithelium and adjacent stromal cells. In ductal carcinoma in situ (DCIS) of the breast, both reduced stromal decorin expression and myxoid stroma are correlated with increased recurrence risk. In this study, we aimed to investigate paracrine regulation of expression of decorin and related extracellular matrix (ECM) proteins in cancer-associated fibroblasts (CAFs). Transforming growth factor-β1 (TGF-β1) was identified as a competent ECM modulator, as it reduced decorin and strongly enhanced versican, biglycan and type I collagen expression...
2014: Oncoscience
Sun-Hee Kim, So Hee Bang, So Yeong Kang, Ki Dae Park, Jun Ho Eom, Il Ung Oh, Si Hyung Yoo, Chan-Wha Kim, Sun Young Baek
Human amniotic membrane-derived stromal cells (hAMSC) are candidates for cell-based therapies. We examined the characteristics of hAMSC including the interaction between hAMSC and breast cancer cells, MCF-7, and MDA-MB-231. Human amniotic membrane-derived stromal cells showed typical MSC properties, including fibroblast-like morphology, surface antigen expression, and mesodermal differentiation. To investigate cell-cell interaction via secreted molecules, we cultured breast cancer cells in hAMSC-conditioned medium (hAMSC-CM) and analyzed their proliferation, migration, and secretome profiles...
February 2015: Tissue & Cell
Noemí Eiró, Juan Sendon-Lago, Samuel Seoane, María A Bermúdez, Maria Luz Lamelas, Tomás Garcia-Caballero, José Schneider, Roman Perez-Fernandez, Francisco J Vizoso
Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion...
November 15, 2014: Oncotarget
Ogunc Meral, Hamdi Uysal
Comparative proteomic analysis of normal and cancer cell lines provides for a better understanding of the molecular mechanism of cancer development and is essential for developing more effective strategies for new biomarker or drug target discovery. The purpose of this study is to compare protein expression levels between fibrosarcoma and fibroblast cell lines. In our study, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques were carried out to compare the protein profile between fibrosarcoma and fibroblast cell lines...
February 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sun-Xia Chen, Xiao-En Xu, Xiao-Qing Wang, Shu-Jian Cui, Lei-Lei Xu, Ying-Hua Jiang, Yang Zhang, Hai-Bo Yan, Qian Zhang, Jie Qiao, Peng-Yuan Yang, Feng Liu
UNLABELLED: Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models...
October 14, 2014: Journal of Proteomics
Rebeca Kawahara, Renato Niyama Lima, Romênia R Domingues, Bianca Alves Pauletti, Gabriela V Meirelles, Michelle Assis, Ana Carolina Migliorini Figueira, Adriana Franco Paes Leme
ADAM17 has been initially identified as the main sheddase responsible for releasing the soluble form of a variety of cell-surface proteins, including growth factors, cytokines, cell adhesion molecules, and receptors, most of which are associated with pathological processes, including cancer and inflammation. However, the function and composition of the ADAM17-dependent secretome on a proteome-wide scale is poorly understood. In this study, we observed that the ADAM17-dependent secretome plays an important role in promoting cell proliferation and migration...
April 4, 2014: Journal of Proteome Research
Jelena Vjetrovic, Pattabhiraman Shankaranarayanan, Marco A Mendoza-Parra, Hinrich Gronemeyer
Senescent cells secrete a plethora of factors with potent paracrine signaling capacity. Strikingly, senescence, which acts as defense against cell transformation, exerts pro-tumorigenic activities through its secretome by promoting tumor-specific features, such as cellular proliferation, epithelial-mesenchymal transition and invasiveness. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has the unique activity of activating cell death exclusively in tumor cells. Given that the senescence-associated secretome (SAS) supports cell transformation, we asked whether SAS factor(s) would establish a program required for the acquisition of TRAIL sensitivity...
June 2014: Aging Cell
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