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cancer associated fibroblasts

Hongfang Zhang, Conghua Xie, Jing Yue, Zhenzhen Jiang, Rongjing Zhou, Ruifei Xie, Yan Wang, Shixiu Wu
Previous studies on the mechanisms underlying ESCC (esophageal squamous cell carcinoma) chemoresistance only focused on tumor cells while tumor microenvironment has been completely ignored. Our study aimed to clarify the effect of CAFs (cancer-associated fibroblasts), one major component of tumor microenvironment, on the chemoresistance of ESCC. By primary culture, two pairs of CAFs and matched NFs (normal fibroblasts) were isolated from tumor tissues of ESCC patients and matched normal esophageal epithelial tissues, respectively...
October 21, 2016: Molecular Carcinogenesis
Priyanka Prajapati, Daniel W Lambert
No abstract text is available yet for this article.
September 2016: Journal of Bone Oncology
Emilie Lukasova, Aleš Kovařík, Alena Bačíková, Martin Falk, Stanislav Kozubek
The cellular transition to senescence is associated with extensive chromatin reorganization and gene expression changes. Recent studies appeared implying an association of lamin B1 (LB1) reduction with chromatin rearrangement in human fibroblasts promoted to senescence, while the mechanisms and structural features of these relations were not yet clarified. In this work we examined the functions of LB1 and lamin B receptor (LBR) in human cancer cells. We found that both LB1 and LBR tend to deplete during cancer cells transfer to senescence by γ-irradiation...
October 19, 2016: Biochemical Journal
Ken Takai, Annie Le, Valerie M Weaver, Zena Werb
Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist...
October 14, 2016: Oncotarget
Marc A Antonyak, Richard A Cerione
Intercellular communication mediated by extracellular vesicles (EVs), membrane-enclosed packages released by cells, plays important roles in several physiological and pathological settings. Moreover, EVs have been shown to contain molecular signatures that reflect their cell of origin, raising the possibility that EV cargo could potentially be used to diagnose disease. However, for this to occur, a better understanding of the differences between EVs generated by normal and diseased cells is needed. We recently discovered that the content and function of one major class of EVs, microvesicles (MVs), changes upon the induction of oncogenic transformation...
October 18, 2016: Small GTPases
Yoshihiro Komohara, Motohiro Takeya
Many non-tumour host cells such as inflammatory cells, fibroblasts and endothelial cells are present in the tumour microenvironment and affect the malignant potential and chemo-resistance of the tumour cells. Macrophages and fibroblasts are the main components of infiltrating stromal cells and are referred to as tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), respectively. TAMs and CAFs are reported to be involved in tumour progression, although their functions change to those of an anti-tumour phenotype under specific conditions...
October 18, 2016: Journal of Pathology
Maximilian Boesch, Sieghart Sopper, Alain G Zeimet, Daniel Reimer, Guenther Gastl, Burkhard Ludewig, Dominik Wolf
Malignancy is fuelled by distinct subsets of stem-like cells which persist under treatment and provoke drug-resistant recurrence. Eradication of these cancer stem cells has therefore become a prime objective for the development and design of novel classes of anti-cancer therapeutics with improved clinical efficacy. Here, we portray potentially clinically-relevant hallmarks of cancer stem cells and focus on their recently appreciated properties of cell variability and plasticity, both of which make them elusive targets for cancer therapies...
October 15, 2016: Biochimica et Biophysica Acta
Gwendal Lazennec, Paula Y Lam
Tumor microenvironment plays a crucial role in coordination with cancer cells in the establishment, growth and dissemination of the tumor. Among cells of the microenvironment, mesenchymal stem cells (MSCs) and their ability to evolve into cancer associated fibroblasts (CAFs) have recently generated a major interest in the field. Numerous studies have described the potential pro- or anti-tumorigenic action of MSCs. The goal of this review is to synthesize recent and emerging discoveries concerning the mechanisms by which MSCs can be attracted to tumor sites, how they can generate CAFs and by which way MSCs are able to modulate the growth, response to treatments, angiogenesis, invasion and metastasis of tumors...
October 14, 2016: Biochimica et Biophysica Acta
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro Perez-Mancera, Sarah E Coupland, Azzam F Taktak, Thomas Bogenrieder, David A Tuveson, Fiona Campbell, Michael C Schmid, Ainhoa Mielgo
Tumor associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors 1 and 2 (IGF), which activate Insulin/IGF receptors on pancreatic cancer cells...
October 14, 2016: Cancer Research
Ameer L Elaimy, Aarif Ahsan, Katherine Marsh, William B Pratt, Dipankar Ray, Theodore S Lawrence, Mukesh K Nyati
Heat shock protein 90 is a chaperone that plays an essential role in the stabilization of a large number of signal transduction molecules, many of which are associated with oncogenesis. An Hsp90 isoform (Hsp90α) has been shown to be selectively phosphorylated on two N-terminal threonine residues (threonine 5 and 7) and is involved in the DNA damage response and apoptosis. However, the kinase that phosphorylates Hsp90α after ionizing radiation (IR) and its role in post-radiation DNA repair remains unclear...
October 11, 2016: Oncotarget
M Moazzem Hossain, Guangyi Zhao, Moon-Sook Woo, James H-C Wang, Jian-Ping Jin
Cell traction force (CTF) plays a critical role in controlling cell shape, enabling cell motility, and maintaining cellular homeostasis in many biological processes such as angiogenesis, development, wound healing, and cancer metastasis. Calponin is an actin filament-associated cytoskeletal protein in smooth muscles and multiple types of non-muscle cells. An established biochemical function of calponin is the inhibition of myosin ATPase in smooth muscle cells. Vertebrates have three calponin isoforms. Among them, calponin 2 is expressed in epithelial cells, endothelial cells, macrophages, myoblasts and fibroblasts, and plays a role in regulating cytoskeleton activities such as cell adhesion, migration and cytokinesis...
October 13, 2016: Biochemistry
Yong-Xu Jia, Teng-Fei Li, Dan-Dan Zhang, Zong-Min Fan, Hui-Jie Fan, Jie Yan, Li-Juan Chen, Hong Tang, Yan-Ru Qin, Xing-Ya Li
Molecular-targeted therapy against tyrosine kinase receptors (RTKs) plays an important role in gastric cancer (GC) treatment. Understanding the correlation between RTK coexpression could better guide clinical drug use. In the present study, the coexpression status of c-MET, fibroblast growth factor receptor 2 (FGFR2), and human epidermal growth factor receptor 2 (HER2) in human GC and their clinical significance in clinical therapy were explored. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction and fluorescent in situ hybridization were performed in 143 cases of GC who had undergone gastrectomy without preoperative chemoradiotherapy...
2016: OncoTargets and Therapy
Roni Allaoui, Caroline Bergenfelz, Sofie Mohlin, Catharina Hagerling, Kiarash Salari, Zena Werb, Robin L Anderson, Stephen P Ethier, Karin Jirström, Sven Påhlman, Daniel Bexell, Balázs Tahin, Martin E Johansson, Christer Larsson, Karin Leandersson
Triple-negative (TN) breast cancers (ER(-)PR(-)HER2(-)) are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment...
October 11, 2016: Nature Communications
Yu Shrike Zhang, Farideh Davoudi, Philipp Walch, Amir Manbachi, Xuan Luo, Valeria Dell'Erba, Amir K Miri, Hassan Albadawi, Andrea Arneri, Xiaoyun Li, Xiaoying Wang, Mehmet Remzi Dokmeci, Ali Khademhosseini, Rahmi Oklu
Pathologic thrombosis kills more people than cancer and trauma combined; it is associated with significant disability and morbidity, and represents a major healthcare burden. Despite advancements in medical therapies and imaging, there is often incomplete resolution of the thrombus. The residual thrombus can undergo fibrotic changes over time through infiltration of fibroblasts from the surrounding tissues and eventually transform into a permanent clot often associated with post-thrombotic syndrome. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial...
October 18, 2016: Lab on a Chip
T Yu, G Yang, Y Hou, X Tang, C Wu, X-A Wu, L Guo, Q Zhu, H Luo, Y-E Du, S Wen, L Xu, J Yin, G Tu, M Liu
Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs...
October 10, 2016: Oncogene
Damien A Leach, Andrew P Trotta, Eleanor F Need, Gail P Risbridger, Renea A Taylor, Grant Buchanan
BACKGROUND: Improving our ability to predict cancer progression and response to conservative or radical intent therapy is critical if we are to prevent under or over treatment of individual patients. Whereas the majority of solid tumors now have a range of molecular and/or immunological markers to help define prognosis and treatment options, prostate cancer still relies mainly on histological grading and clinical parameters. We have recently reported that androgen receptor (AR) expression in stroma inversely associates with prostate cancer-specific survival, and that stromal AR reduces metastasis...
October 8, 2016: Prostate
Yanbo Liu, Wanguo Yang, Lijing Zhao, Zuowen Liang, Weigao Shen, Qinlong Hou, Zhenjiang Wang, Jing Jiang, Sun Ying
BACKGROUND: Bladder cancer, cystitis and bladder polyp are the most common urinary system diseases all over the world. Our former research results show that IL-17A and IL-17 F contribute to the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer (Pca) while IL-17E interacting with IL-17RB might have an anti-tumor effect. RESULTS: Using imunohistochemistry, we systemically compared immunoreactivity of ligands (IL-17A, E and F) and receptors (IL-17RA, IL-17RB and IL-17RC) of IL-17 family, infiltration of inflammatory cells and changes of structural cells (fibroblast cells, smooth muscle and vascular endothelial cells) in sections of bladder tissues from subjects with bladder cancer, cystitis and bladder polyp...
October 3, 2016: BMC Immunology
Piotr Donizy, Maciej Kaczorowski, Przemyslaw Biecek, Agnieszka Halon, Teresa Szkudlarek, Rafal Matkowski
GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS)...
October 1, 2016: International Journal of Molecular Sciences
Heather M Brechbuhl, Jessica Finlay-Schultz, Tomomi Yamamoto, Austin Gillen, Diana M Cittelly, Aik-Choon Tan, Sharon B Sams, Manoj Pillai, Anthony Elias, William A Robinson, Carol A Sartorius, Peter Kabos
PURPOSE: Anti-endocrine therapy remains the most effective treatment for ER+ breast cancer, but development of resistance is a major clinical complication. Effective targeting of mechanisms that control the loss of ER dependency in breast cancer remains elusive. We analyzed breast cancer-associated fibroblasts (CAFs), the largest component of the tumor microenvironment, as a factor contributing to ER expression levels and anti-endocrine resistance. EXPERIMENTAL DESIGN: Tissues from ER+ breast cancer patients were analyzed for the presence of CD146 positive (CD146pos) and CD146 negative (CD146neg) fibroblasts...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Julie Leca, Sébastien Martinez, Sophie Lac, Jérémy Nigri, Véronique Secq, Marion Rubis, Christian Bressy, Arnauld Sergé, Marie-Noelle Lavaut, Nelson Dusetti, Céline Loncle, Julie Roques, Daniel Pietrasz, Corinne Bousquet, Stéphane Garcia, Samuel Granjeaud, Mehdi Ouaissi, Jean Baptiste Bachet, Christine Brun, Juan L Iovanna, Pascale Zimmermann, Sophie Vasseur, Richard Tomasini
The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk...
October 4, 2016: Journal of Clinical Investigation
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