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Carcinoma-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
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
K Steinhäuser, P Klöble, N-N Kreis, A Ritter, A Friemel, S Roth, J M Reichel, J Michaelis, M A Rieger, F Louwen, F Oswald, J Yuan
Deregulation of mitotic microtubule (MT) dynamics results in defective spindle assembly and chromosome missegregation, leading further to chromosome instability, a hallmark of tumor cells. RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signaling pathway. Intriguingly, deregulated RITA is involved in primary hepatocellular carcinoma and other malignant entities. We were interested in the potential molecular mechanisms behind its involvement. We show here that RITA binds to tubulin and localizes to various mitotic MT structures...
October 10, 2016: Oncogene
Himalaya Parajuli, Muy-Teck Teh, Siren Abrahamsen, Ingrid Christoffersen, Evelyn Neppelberg, Stein Lybak, Tarig Osman, Anne Chr Johannessen, Donald Gullberg, Kathrine Skarstein, Daniela Elena Costea
BACKGROUND: Cancer-associated fibroblasts (CAFs) were shown to be important for tumour progression in head and neck squamous cell carcinomas (HNSCCs). Their heterogeneity and lack of specific markers is increasingly recognized. Integrin α11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker. AIM: To investigate integrin α11 expression and its correlation with the expression of a well-known marker of CAF, alpha smooth muscle actin (α-SMA), in HNSCC...
October 4, 2016: Journal of Oral Pathology & Medicine
Xavier Catteau, Philippe Simon, Frédéric Buxant, Jean-Christophe Noël
Cancer- associated fibroblasts (CAFs) are actively involved in breast carcinoma. Our previous study demonstrated that the majority of these CAFs were smooth muscle actin (SMA) positive and were therefore termed peritumoral myofibroblast (PMY). Glucocorticoid, linked or not with its receptor (GR), has been postulated to serve a major role in normal breast and breast carcinoma; however, their role in CAFs remains poorly understood. The aim of the present study was to assess the presence of GR in breast CAFs and particularly in PMY in 56 cases of invasive breast carcinoma in correlation with clinicopathological parameters, by immunohistochemistry...
October 2016: Molecular and Clinical Oncology
Jine Yang, Yang Lu, Ying-Ying Lin, Zhi-Yuan Zheng, Jian-Hong Fang, Shuai He, Shi-Mei Zhuang
Vascular mimicry (VM) describes the phenomenon that tumor cells but not endothelial cells form vascular-like channels, which provide blood perfusion for tumor tissues. VM is associated with tumor growth, metastasis and worse survival of different cancers. The mechanisms of VM formation remain largely unknown. We showed that the conditioned medium of cancer-associated fibroblast (CM-CAF) promoted tumor cells to form capillary-like structure in vitro. Consistently, co-implantation of CAFs with tumor cells significantly enhanced VM formation in mouse xenografts, and higher amount of CAFs was found in VM(+) human HCC tissues compared to VM(-) ones...
September 28, 2016: Cancer Letters
Jason D Domogauer, Sonia M de Toledo, Edouard I Azzam
Understanding the early heterotypic interactions between cancer cells and the surrounding non-cancerous stroma is important in elucidating the events leading to stromal activation and establishment of the tumor microenvironment (TME). Several in vitro and in vivo models of the TME have been developed; however, in general these models do not readily permit isolation of individual cell populations, under non-perturbing conditions, for further study. To circumvent this difficulty, we have employed an in vitro TME model using a cell growth substrate consisting of a permeable microporous membrane insert that permits simple generation of highly enriched cell populations grown intimately, yet separately, on either side of the insert's membrane for extended co-culture times...
2016: Journal of Visualized Experiments: JoVE
Sharon J Akrish, Adi Rachmiel, Edmond Sabo, Marilena Vered, Ofer Ben-Izhak
BACKGROUND: Cancer-associated fibroblasts (CAFs) are generally associated with negative prognostic factors. This study compares the clinicopathologic impact of CAFs in oral squamous cell carcinoma in patients with a history of proliferative verrucous leukoplakia (p-scca) and patients with conventional squamous cell carcinoma of the buccal mucosa, gingiva, and palate (c-scca). METHODS: A retrospective clinicopathologic and immunohistochemical analysis of 97 tumor specimens from 78 patients (13 patients with proliferative verrucous leukoplakia-associated squamous cell carcinoma (n = 32) and conventional squamous cell carcinoma from the buccal mucosa, gingiva, and palate (n = 65) was conducted...
September 29, 2016: Journal of Oral Pathology & Medicine
Tao Wang, Faiyaz Notta, Roya Navab, Joella Joseph, Emin Ibrahimov, Jing Xu, Chang-Qi Zhu, Ayelet Borgida, Steven Gallinger, Ming-Sound Tsao
: Carcinoma associated fibroblasts (CAFs) represent a significant component of pancreatic cancer stroma and are biologically implicated in tumour progression. However, evidence of both cancer promoting and restraining properties amongst CAFs suggests the possibility of multiple phenotypic subtypes. Here, it is demonstrated that senescent CAFs promote pancreatic cancer invasion and metastasis compared to non-senescent control CAFs using in vitro transwell invasion models and in vivo xenograft mouse models...
September 27, 2016: Molecular Cancer Research: MCR
Andriy Marusyk, Doris Tabassum, Michalina Janiszewska, Andrew Place, Anne Trinh, Andrii I Rozhok, Saumyadipta Pyne, Jennifer Guerriero, Shaokun Shu, Muhammad Ekram, Alexander Ishkin, Daniel P Cahill, Yuri Nikolsky, Timothy A Chan, Mothaffar F Rimawi, Susan G Hilsenbeck, Rachel Schiff, C Kent Osborne, Anthony Letai, Kornelia Polyak
Using a 3D co-culture model, we identified significant sub-type-specific changes in gene expression, metabolic, and therapeutic sensitivity profiles of breast cancer cells in contact with cancer-associated fibroblasts (CAFs). CAF-induced gene expression signatures predicted clinical outcome and immune-related differences in the microenvironment. We found that fibroblasts strongly protect carcinoma cells from lapatinib, attributable to its reduced accumulation in carcinoma cells and an elevated apoptotic threshold...
September 26, 2016: Cancer Research
Philipp H Baldia, Angela Maurer, Timon Heide, Michael Rose, Robert Stoehr, Arndt Hartmann, Sarah V Williams, Margaret A Knowles, Ruth Knuechel, Nadine T Gaisa
Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis)...
September 22, 2016: Oncotarget
Katarzyna Ratajczak-Wielgomas, Jedrzej Grzegrzolka, Aleksandra Piotrowska, Agnieszka Gomulkiewicz, Wojciech Witkiewicz, Piotr Dziegiel
Periostin (POSTN) is a secreted cell adhesion glycoprotein that plays an important role in proliferation, adhesion and migration processes, as well as in regulation of mechanisms related to epithelial-mesenchymal transition (EMT). It also plays a key role in angio- and lymphangiogenesis and in formation of distant metastases. The aim of this work was to determine expression of POSTN in invasive ductal breast carcinoma (IDC) and in non-invasive ductal carcinoma in situ (DCIS) and to correlate its expression with clinicopathological parameters...
September 15, 2016: Oncology Reports
Eduard Ling, Amit Ringel, Ina Sigal-Batikoff, Naim Abu-Freha, Hananya Vaknine, Wledy Friah, Avraham Reshef, Ilia Pinsk, Alexander Fich, Sergio Lamprecht
BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) play an important role in tumor development and progression. The prevailing consensus favors the view that a specific epigenetic signature underpins the stable CAF phenotype. The aim of the present study was to assess global DNA methylation in CAFs during the adenoma-carcinoma sequence in non-familial sporadic human colorectal cancer (CRC). PATIENTS AND METHODS: Immunohistochemical staining of nuclear 5-methylcytosine (5'-meCyt) was performed in matched samples of colonic tumor tissue and normal colonic mucosa excised from six patients with adenomas and four with adenocarcinomas...
September 2016: Anticancer Research
Li-Ching Fan, Yung-Ming Jeng, Yueh-Tong Lu, Huang-Chun Lien
In addition to contraction, myoepithelia have diverse paracrine effects, including a tumor suppression effect. However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to contractile myofibroblasts. We investigated whether TGF-β can upregulate potential myoepithelial markers, which may have functional and clinicopathological significance in breast cancer. We found that TGF-β induced SPOCK1 expression in MCF10A, MCF12A, and M10 breast cells and demonstrated SPOCK1 as a novel myoepithelial marker that was immunolocalized within or beneath myoepithelia lining ductolobular units...
2016: PloS One
Milind Javle, Tanios Bekaii-Saab, Apurva Jain, Ying Wang, Robin Katie Kelley, Kai Wang, Hyunseon C Kang, Daniel Catenacci, Siraj Ali, Sunil Krishnan, Daniel Ahn, Andrea Grace Bocobo, Mingxin Zuo, Ahmed Kaseb, Vincent Miller, Philip J Stephens, Funda Meric-Bernstam, Rachna Shroff, Jeffrey Ross
BACKGROUND: Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit. METHODS: Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 412 intrahepatic cholangiocarcinomas (IHCCAs), 57 extrahepatic cholangiocarcinomas (EHCCAs), and 85 gallbladder carcinomas (GBCAs). The mutational profile was correlated with the clinical outcome of standard and experimental therapies for 321 patients...
September 13, 2016: Cancer
Ai Kanemaru, Koji Yamamoto, Makiko Kawaguchi, Tsuyoshi Fukushima, Chen-Yong Lin, Michael D Johnson, Eric Camerer, Hiroaki Kataoka
Cancer-associated fibroblasts (CAFs) are known to contribute to cancer progression. We have reported that cell surface expression of hepatocyte growth factor activator inhibitor 1 (HAI-1) is decreased in invasive oral squamous cell carcinoma (OSCC) cells. This study examined if HAI-1-insufficiency contributes to CAF recruitment in OSCC. Serum-free conditioned medium (SFCM) from a human OSCC line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB, MRC5 and KD. SFCM from HAI-1-knockdown SAS showed an additive effect on the migration of NB1RGB and MRC5, but not KD...
September 12, 2016: International Journal of Cancer. Journal International du Cancer
Dongyu Jia, Zhenqiu Liu, Nan Deng, Tuan Zea Tan, Ruby Yun-Ju Huang, Barbie Taylor-Harding, Dong-Joo Cheon, Kate Lawrenson, Wolf R Wiedemeyer, Ann E Walts, Beth Y Karlan, Sandra Orsulic
Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated CAFs from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second, it is unclear whether CAFs in different organs have different molecular and functional properties that necessitate organ-specific therapeutic designs...
September 5, 2016: Cancer Letters
Peng Wang, Li-Zhu Jiang, Bin Xue
BACKGROUND: Recombinant human endostatin (Endostar) has been widely used to suppress angiogenesis in carcinoma patients. Hypertrophic scar (HS) tissue, much like a carcinoma, is often associated with angiogenesis. However, there have been few studies conducted on the effects of Endostar on HS or its mechanism. OBJECTIVE: This paper investigated the effects Endostar on the HS of rabbit ears and studied the effects of Endostar on VEGF and TIMP-1 expression. METHODS: Sixteen New Zealand white rabbits were used to establish HS models...
June 2016: African Health Sciences
Giuseppe Merlino, Patrizia Miodini, Biagio Paolini, Maria Luisa Carcangiu, Massimiliano Gennaro, Matteo Dugo, Maria Grazia Daidone, Vera Cappelletti
BACKGROUND: The tumor microenvironment participates in the regulation of tumor progression and influences treatment sensitivity. In breast cancer, it also may play a role in determining the fate of non-invasive lesions such as ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive diseases, which is aggressively treated despite its indolent nature in many patients since no biomarkers are available to predict the progression of DCIS to invasive disease. In vitro models of stromal activation by breast tumor cells might provide clues as to specific stromal genes crucial for the transition from DCIS to invasive disease...
2016: Microarrays
Masahito Naito, Keiju Aokage, Kouichi Saruwatari, Kakeru Hisakane, Tomohiro Miyoshi, Tomoyuki Hishida, Junji Yoshida, Sugano Masato, Motohiro Kojima, Takeshi Kuwata, Satoshi Fujii, Atsushi Ochiai, Yukitoshi Sato, Masahiro Tsuboi, Genichiro Ishii
OBJECTIVES: Invasive lepidic predominant adenocarcinoma (LPA) of the lung is thought to progress in a stepwise fashion from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). The aim of this study was to investigate the microenvironmental changes during the development from AIS to LPA. MATERIALS AND METHODS: Clinicopathological characteristics of AIS (n=51), MIA (n=59), LPA smaller than 3cm (LPA-S, n=113), and LPA larger than 3cm (LPA-L, n=47) were analyzed...
October 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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