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fibroblast cancer cell secretomes

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https://www.readbyqxmd.com/read/29750999/modeling-triple-negative-breast-cancer-heterogeneity-effects-of-stromal-macrophages-fibroblasts-and-tumor-vasculature
#1
Kerri-Ann Norton, Kideok Jin, Aleksander S Popel
A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells...
May 8, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29681158/proteomic-analysis-of-cancer-associated-fibroblasts-reveal-a-paracrine-role-for-mfap5-in-human-oral-tongue-squamous-cell-carcinoma
#2
Simona Principe, Salvador Mejia-Guerrero, Vladimir Ignatchenko, Ankit Sinha, Alex Ignatchenko, Wei Shi, Keira Pereira, Susie Su, Shao Hui Huang, Brian O'Sullivan, Wei Xu, David Goldstein, Ilan Weinreb, Laurie Ailles, Fei-Fei Liu, Thomas Kislinger
Bidirectional communication between cells and their microenvironment is crucial for both normal tissue homeostasis and tumor growth. During the development of oral tongue squamous cell carcinoma (OTSCC), cancer-associated fibroblasts (CAFs) create a supporting niche by maintaining a bidirectional crosstalk with cancer cells, mediated by classically secreted factors and various nanometer-sized vesicles, termed as extracellular vesicles (EVs). To better understand the role of CAFs within the tumor stroma and elucidate the mechanism by which secreted proteins contribute to OTSCC progression, we isolated and characterized patient-derived CAFs from resected tumors with matched adjacent tissue fibroblasts (AFs)...
April 22, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29669735/ctgf-vegfa-activated-fibroblasts-promote-tumor-migration-through-micro-environmental-modulation
#3
Wei Wu, Esther A Zaal, Celia R Berkers, Simone Lemeer, Albert J R Heck
Fibroblast activation is associated with tumour progression and implicated in metastasis, but the initial triggering signals required to kick-start this process remain largely unknown. Since small cancerous lesions share limited physical contact with neighboring fibroblasts, we reasoned the first tumour-derived signal for fibroblast activation should be secreted and diffusible. By pulsed metabolic labeling and click-chemistry based affinity enrichment, we sieved through the ductal carcinoma secretome for potential fibroblast activators...
April 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29580188/ovarian-cancer-derived-extracellular-vesicles-affect-normal-human-fibroblast-behavior
#4
Ilaria Giusti, Marianna Di Francesco, Sandra D'Ascenzo, Maria Grazia Palmerini, Guido Macchiarelli, Gaspare Carta, Vincenza Dolo
It has become clear that non-tumor cells in the microenvironment, especially fibroblasts, actively participate in tumor progression. Fibroblasts conditioned by tumor cells become "activated" and, as such, are identified as CAFs (cancer-associated fibroblasts). These CAFs remodel the tumor stroma to make it more favourable for cancer progression. The aim of this work was to verify whether EVs (extracellular vesicles - whose role as mediators of information between tumor and stromal cells is well known) released from human ovarian cancer cells were able to activate fibroblasts...
March 26, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29558956/mir-16-regulates-the-pro-tumorigenic-potential-of-lung-fibroblasts-through-the-inhibition-of-hgf-production-in-an-fgfr-1-and-mek1-dependent-manner
#5
Francesca Andriani, Maria Teresa Majorini, Miguel Mano, Elena Landoni, Rosalba Miceli, Federica Facchinetti, Mavis Mensah, Enrico Fontanella, Matteo Dugo, Mauro Giacca, Ugo Pastorino, Gabriella Sozzi, Domenico Delia, Luca Roz, Daniele Lecis
BACKGROUND: Fibroblasts are crucial mediators of tumor-stroma cross-talk through synthesis and remodeling of the extracellular matrix and production of multiple soluble factors. Nonetheless, little is still known about specific determinants of fibroblast pro-tumorigenic activity in lung cancer. Here, we aimed at understanding the role of miRNAs, which are often altered in stromal cells, in reprogramming fibroblasts towards a tumor-supporting phenotype. METHODS: We employed a co-culture-based high-throughput screening to identify specific miRNAs modulating the pro-tumorigenic potential of lung fibroblasts...
March 20, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29275043/signatures-of-protein-expression-revealed-by-secretome-analyses-of-cancer-associated-fibroblasts-and-melanoma-cell-lines
#6
Tarcísio Liberato, Dayelle S Pessotti, Isabella Fukushima, Eduardo S Kitano, Solange M T Serrano, André Zelanis
The imbalance of cellular homeostasis during oncogenesis together with the high heterogeneity of tumor-associated stromal cells have a marked effect on the repertoire of the proteins secreted by malignant cells (the secretome). Hence, the study of tumoral secretomes provides insights for understanding the cross-talk between cells within the tumor microenvironment as well as the key effectors for the establishment of the pre-metastatic niche in distant tumor sites. In this context, we performed a proteomic analysis of the secretomes derived from four cell lines: a paired set of fibroblasts - Hs 895...
March 1, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29184429/topical-application-of-st266-reduces-uv-induced-skin-damage
#7
Linna Guan, Amanda Suggs, Emily Galan, Minh Lam, Elma D Baron
Ultraviolet radiation (UVR) has a significant impact on human skin and is the major environmental factor for skin cancer formation. It is also believed that 80% of the signs of skin aging are attributed to UVR. UVR induces inflammatory changes in the skin via the increase in oxidative stress, DNA damage vascular permeability, and fluctuation in a myriad of cytokines. Acutely, UVR causes skin inflammation and DNA damage, which manifest as sunburn (erythema). ST266 is the secretome of proprietary amnion-derived cells that have been shown to reduce inflammation and accelerate healing of various wounds by promoting migration of keratinocytes and fibroblasts in preclinical animal studies...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/29157176/separation-of-cell-survival-growth-migration-and-mesenchymal-transdifferentiation-effects-of-fibroblast-secretome-on-tumor-cells-of-head-and-neck-squamous-cell-carcinoma
#8
Veronika Maria Metzler, Christian Pritz, Anna Riml, Angela Romani, Raphaela Tuertscher, Teresa Steinbichler, Daniel Dejaco, Herbert Riechelmann, József Dudás
Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast-secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial-mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29140428/hpv-negative-but-not-hpv-positive-oropharyngeal-carcinomas-induce-fibroblasts-to-support-tumour-invasion-through-micro-environmental-release-of-hgf-and-il-6
#9
Robert Bolt, Bernadette Foran, Craig Murdoch, Daniel W Lambert, Sally Thomas, Keith D Hunter
Human papillomavirus (HPV) infection is causally related to a subset of oropharyngeal carcinomas (OPC) and is linked to a more favourable prognosis compared to HPV-negative OPC. The mechanisms underlying this effect on prognosis are not fully understood, but interactions with the tumour microenvironment may be pivotal. Here, we investigated the role of the tumour microenvironment in HPV-positive compared to HPV-negative cancer using 2D and 3D modelling of OPC interactions with stromal fibroblasts. HPV-negative, but not HPV-positive, OPC-derived cell lines induced a rapid fibroblast secretory response that supported 2D cancer cell migration and invasion in vitro...
February 9, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/28974015/the-epithelial-to-mesenchymal-transition-in-breast-cancer-focus-on-basal-like-carcinomas
#10
REVIEW
Monica Fedele, Laura Cerchia, Gennaro Chiappetta
Breast cancer is a heterogeneous disease that is characterized by a high grade of cell plasticity arising from the contribution of a diverse range of factors. When combined, these factors allow a cancer cell to transition from an epithelial to a mesenchymal state through a process of dedifferentiation that confers stem-like features, including chemoresistance, as well as the capacity to migrate and invade. Understanding the complex events that lead to the acquisition of a mesenchymal phenotype will therefore help to design new therapies against metastatic breast cancer...
September 30, 2017: Cancers
https://www.readbyqxmd.com/read/28837246/c-jun-n-terminal-kinase-in-pancreatic-tumor-stroma-augments-tumor-development-in-mice
#11
Takeshi Sato, Wataru Shibata, Yohko Hikiba, Yoshihiro Kaneta, Nobumi Suzuki, Sozaburo Ihara, Yasuaki Ishii, Soichiro Sue, Eri Kameta, Makoto Sugimori, Hiroaki Yamada, Hiroaki Kaneko, Tomohiko Sasaki, Tomohiro Ishii, Toshihide Tamura, Masaaki Kondo, Shin Maeda
Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease and there is an urgent need to develop improved therapeutic approaches. The role of c-Jun N-terminal kinase (JNK) in PDAC stroma is not well defined even though dense desmoplastic reactions are characteristic of PDAC histology. We aimed to explore the role of JNK in PDAC stroma in mice. We crossed Ptf1aCre/+ ;KrasG12D/+ mice with JNK1-/- mice to generate Ptf1aCre/+ ;KrasG12D/+ ;JNK1-/- (Kras;JNK1-/- ) mice. Tumor weight was significantly lower in Kras;JNK1-/- mice than in Kras;JNK1+/- mice, whereas histopathological features were similar...
November 2017: Cancer Science
https://www.readbyqxmd.com/read/28510269/kallikrein-related-peptidase-4-induces-cancer-associated-fibroblast-features-in-prostate-derived-stromal-cells
#12
Thomas Kryza, Lakmali M Silva, Nathalie Bock, Ruth A Fuhrman-Luck, Carson R Stephens, Jin Gao, Hema Samaratunga, Mitchell G Lawrence, John D Hooper, Ying Dong, Gail P Risbridger, Judith A Clements
The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface...
October 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28420162/hepatocyte-growth-factor-a-key-tumor-promoting-factor-in-the-tumor-microenvironment
#13
REVIEW
Benjamin Yaw Owusu, Robert Galemmo, James Janetka, Lidija Klampfer
The tumor microenvironment plays a key role in tumor development and progression. Stromal cells secrete growth factors, cytokines and extracellular matrix proteins which promote growth, survival and metastatic spread of cancer cells. Fibroblasts are the predominant constituent of the tumor stroma and Hepatocyte Growth Factor (HGF), the specific ligand for the tyrosine kinase receptor c-MET, is a major component of their secretome. Indeed, cancer-associated fibroblasts have been shown to promote growth, survival and migration of cancer cells in an HGF-dependent manner...
April 17, 2017: Cancers
https://www.readbyqxmd.com/read/28273155/tumor-stroma-with-senescence-associated-secretory-phenotype-in-steatohepatitic-hepatocellular-carcinoma
#14
Jee San Lee, Jeong Eun Yoo, Haeryoung Kim, Hyungjin Rhee, Myoung Ju Koh, Ji Hae Nahm, Jin Sub Choi, Kee-Ho Lee, Young Nyun Park
Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28198360/secreted-clic3-drives-cancer-progression-through-its-glutathione-dependent-oxidoreductase-activity
#15
Juan R Hernandez-Fernaud, Elena Ruengeler, Andrea Casazza, Lisa J Neilson, Ellie Pulleine, Alice Santi, Shehab Ismail, Sergio Lilla, Sandeep Dhayade, Iain R MacPherson, Iain McNeish, Darren Ennis, Hala Ali, Fernanda G Kugeratski, Heba Al Khamici, Maartje van den Biggelaar, Peter V E van den Berghe, Catherine Cloix, Laura McDonald, David Millan, Aoisha Hoyle, Anna Kuchnio, Peter Carmeliet, Stella M Valenzuela, Karen Blyth, Huabing Yin, Massimiliano Mazzone, Jim C Norman, Sara Zanivan
The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2)...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/27907906/senescent-fibroblast-derived-chemerin-promotes-squamous-cell-carcinoma-migration
#16
Vida Farsam, Abhijit Basu, Martina Gatzka, Nicolai Treiber, Lars A Schneider, Medhanie A Mulaw, Tanja Lucas, Stefan Kochanek, Reinhard Dummer, Mitchell P Levesque, Meinhard Wlaschek, Karin Scharffetter-Kochanek
Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27797378/stromal-pten-inhibits-the-expansion-of-mammary-epithelial-stem-cells-through-jagged-1
#17
G M Sizemore, S Balakrishnan, A M Hammer, K A Thies, A J Trimboli, J A Wallace, S T Sizemore, R D Kladney, S A Woelke, L Yu, S A Fernandez, A Chakravarti, G Leone, M C Ostrowski
Fibroblasts within the mammary tumor microenvironment are active participants in carcinogenesis mediating both tumor initiation and progression. Our group has previously demonstrated that genetic loss of phosphatase and tensin homolog (PTEN) in mammary fibroblasts induces an oncogenic secretome that remodels the extracellular milieu accelerating ErbB2-driven mammary tumor progression. While these prior studies highlighted a tumor suppressive role for stromal PTEN, how the adjacent normal epithelium transforms in response to PTEN loss was not previously addressed...
April 20, 2017: Oncogene
https://www.readbyqxmd.com/read/27725197/in-vitro-secretomics-study-of-pterygium-derived-fibroblasts-by-itraq-based-quantitative-proteomics-strategy
#18
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...
December 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27605433/secreted-primary-human-malignant-mesothelioma-exosome-signature-reflects-oncogenic-cargo
#19
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
https://www.readbyqxmd.com/read/27324842/transformed-mdck-cells-secrete-elevated-mmp1-that-generates-lama5-fragments-promoting-endothelial-cell-angiogenesis
#20
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
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