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Carcinoma-Associated Fibroblasts

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https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#1
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773427/microphthalmia-associated-transcription-factor-mitf-promiscuous-staining-patterns-in-fibrohistiocytic-lesions-is-a-potential-pitfall
#2
Sambit K Mohanty, Shivani Sharma, Dinesh Pradhan, Shivani R Kandukuri, Navid Farahani, Catherine Barry, Julie M Wu, David Frishberg, Bonnie Balzer
Microphthalmia-associated transcription factor (MiTF) is used as a marker of melanocytic differentiation. However, MiTF immunoexpression has also been observed in histiocytes, macrophages, smooth muscle cells and fibroblasts, which raise the concern of fibrohistiocytic (FH) lesions being misdiagnosed as melanoma based on MiTF immunoreactivity. MiTF has been known to be positive in FH tumors, but this is the first study evaluating ninety-three fibrohistiocytic neoplasms to understand and delineate the staining pattern of MiTF in these tumors...
May 11, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29769197/cancer-associated-fibroblasts-drive-glycolysis-in-a-targetable-signaling-loop-implicated-in-head-and-neck-squamous-cell-carcinoma-progression
#3
Dhruv Kumar, Jacob New, Vikalp Vishwakarma, Radhika Joshi, Jonathan Enders, Fangchen Lin, Sumana Dasari, Wade R Gutierrez, George Leef, Sivapriya Ponnurangam, Hemantkumar Chavan, Lydia Ganaden, Mackenzie M Thornton, Hongying Dai, Ossama Tawfik, Jeffrey Straub, Yelizaveta Shnayder, Kiran Kakarala, Terance Ted Tsue, Douglas A Girod, Bennett Van Houten, Shrikant Anant, Partha Krishnamurthy, Sufi Mary Thomas
Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted hepatocyte growth factor (HGF) facilitates HNSCC progression, however very little is known about the role of CAFs in HNSCC metabolism. Here we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#4
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29753678/deficiency-of-fibroblast-growth-factor-21-fgf21-promotes-hepatocellular-carcinoma-hcc-in-mice-on-a-long-term-obesogenic-diet
#5
Garima Singhal, Gaurav Kumar, Suzanne Chan, Ffolliott M Fisher, Yong Ma, Hilde G Vardeh, Imad A Nasser, Jeffrey S Flier, Eleftheria Maratos-Flier
OBJECTIVE: Non-alcoholic fatty liver (NAFL) associated with obesity is a major cause of liver diseases which can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) plays an important role in liver metabolism and is also a potential marker for NAFL. Here we aimed to test the effect of FGF21 deficiency on liver pathology in mice consuming a conventional high fat, high sucrose (HFHS) obesogenic diet for up to 52 weeks...
March 8, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29753013/transferrin-anchored-poly-lactide-micelles-to-improve-anticancer-activity-of-curcumin-in-hepatic-and-cervical-cancer-cell-monolayers-and-3d-spheroids
#6
Preeti Kumari, Sri Vishnu Kiran Rompicharla, Omkara Swami Muddineti, Balaram Ghosh, Swati Biswas
In recent years, actively targeted drug delivery systems have been utilized in pre-clinical studies for site-specific delivery of drugs, which reduces toxicities associated with chemotherapy. This study reports the preparation of the tumor homing ligand, transferrin (Tf) anchored methoxy-polyethylene glycol-poly(d,l-lactide) polymeric micelles (Tf-PP). Curcumin which possess wide anti-cancer activity was loaded into the micelles. Tf-PPC with average particle size of 132.16 ± 1.3 nm and encapsulation efficiency of 88...
May 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29743718/expressional-analysis-of-disease-relevant-signalling-pathways-in-primary-tumours-and-metastasis-of-head-and-neck-cancers
#7
Dorothee Goesswein, Negusse Habtemichael, Aslihan Gerhold-Ay, Johanna Mazur, Désirée Wünsch, Shirley K Knauer, Julian Künzel, Christoph Matthias, Sebastian Strieth, Roland H Stauber
Head and neck squamous cell carcinoma (HNSCC) often metastasize to lymph nodes resulting in poor prognosis for patients. Unfortunately, the underlying molecular mechanisms contributing to tumour aggressiveness, recurrences, and metastasis are still not fully understood. However, such knowledge is key to identify biomarkers and drug targets to improve prognosis and treatments. Consequently, we performed genome-wide expression profiling of 15 primary HNSSCs compared to corresponding lymph node metastases and non-malignant tissue of the same patient...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29734861/establishment-and-characterization-of-a-carcinoma-associated-fibroblast-cell-line-derived-from-a-human-salivary-gland-adenoid-cystic-carcinoma
#8
Jing Kong, Han Zhao, Qianhui Shang, Zhifei Ma, Ni Kang, Junling Tan, Hyat Ahmed Ibrahim Alraimi, Tingjiao Liu
Salivary gland adenoid cystic carcinoma (SACC) is one of the most common malignancies in the oral and maxillofacial region. Carcinoma-associated fibroblast (CAF) is an important component in the tumor microenvironment and participates in SACC progression. In this study, we established a CAF cell line derived from a human SACC and named it CAF-SA. It was identified that CAF-SA expressed typical CAF biomarkers. Then, we studied the cellular communications between CAF-SA, tumor cells and endothelial cells. It was found that CAF-SA promoted the migration, invasion, and proliferation of SACC tumor cells in vitro...
December 2018: Cell Communication & Adhesion
https://www.readbyqxmd.com/read/29731961/macrophages-induce-budding-in-aggressive-human-colon-cancer-subtypes-by-protease-mediated-disruption-of-tight-junctions
#9
Kari Trumpi, Nicola Frenkel, Timo Peters, Nicoline M Korthagen, Jennifer M J Jongen, Daniëlle Raats, Helma van Grevenstein, Yara Backes, Leon M Moons, Miangela M Lacle, Jan Koster, Danny Zwijnenburg, Inne H M Borel Rinkes, Onno Kranenburg
Primary human colorectal tumors with a high stromal content have an increased capacity to metastasize. Cancer-associated fibroblasts (CAFs) promote metastasis, but the contribution of other stromal cell types is unclear. Here we searched for additional stromal cell types that contribute to aggressive tumor cell behavior. By making use of the 'immunome compendium'-a collection of gene signatures reflecting the presence of specific immune cell-types-we show that macrophage signatures are most strongly associated with a high CAF content and with poor prognosis in multiple large cohorts of primary tumors and liver metastases...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29728125/matrix-stiffness-upregulated-loxl2-promotes-fibronectin-production-mmp9-and-cxcl12-expression-and-bmdcs-recruitment-to-assist-pre-metastatic-niche-formation
#10
Sifan Wu, Qiongdan Zheng, Xiaoxia Xing, Yinying Dong, Yaohui Wang, Yang You, Rongxin Chen, Chao Hu, Jie Chen, Dongmei Gao, Yan Zhao, Zhiming Wang, Tongchun Xue, Zhenggang Ren, Jiefeng Cui
BACKGROUND: Higher matrix stiffness affects biological behavior of tumor cells, regulates tumor-associated gene/miRNA expression and stemness characteristic, and contributes to tumor invasion and metastasis. However, the linkage between higher matrix stiffness and pre-metastatic niche in hepatocellular carcinoma (HCC) is still largely unknown. METHODS: We comparatively analyzed the expressions of LOX family members in HCC cells grown on different stiffness substrates, and speculated that the secreted LOXL2 may mediate the linkage between higher matrix stiffness and pre-metastatic niche...
May 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29723887/-lidline-tattoo-associated-with-basal-cell-carcinoma-of-the-lid-margin-coincidence-or-association
#11
Elisabeth M Messmer, Caroline Möhring-Bengisu, Christina Miller
A cystic lesion of the lid margin was excised suspecting basal cell carcinoma. On histology, black-turquoise pigment was seen in the dermis adjacent to the basal cell carcinoma. It was pronounced perivascular, intracellular in macrophages and fibroblasts, but also extracellular as free pigment in the tissue, compatible with an eyelid line tattoo. Typical tissue reactions to tattoo ink, meibomian gland dysfunction after lid margin tattoo, as well as inflammatory reactions in the retina and choroid associated with tattoos distant from the eye are discussed...
May 3, 2018: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/29721182/crosstalk-between-akt-signaling-and-cold-shock-proteins-in-mediating-invasive-cell-phenotypes
#12
Raphael Hohlfeld, Sabine Brandt, Anja Bernhardt, Xenia Gorny, Daniel Schindele, Burkhard Jandrig, Martin Schostak, Berend Isermann, Jonathan A Lindquist, Peter R Mertens
Cold shock proteins are up-regulated by cellular stress and orchestrate inflammatory responses, cell proliferation, and differentiation. Enhanced cold shock protein expression promotes malignant cell transformation; up-regulation is detected in most cancers and associated with poor prognosis. Akt1, a serine/threonine kinase, is a potent oncogene, which activates pro-proliferative and anti-apoptotic signaling pathways, and phosphorylates the cold shock domain. Unexpectedly, chicken-YB-1 abrogates PI3K-Akt-dependent oncogenic cell transformation in embryonic fibroblasts...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719198/interaction-between-oral-squamous-cell-carcinoma-cells-and-fibroblasts-through-tgf-%C3%AE-1-mediated-by-podoplanin
#13
Yao-Yin Li, Chuan-Xiang Zhou, Yan Gao
Podoplanin is upregulated in the invasive front of oral squamous cell carcinoma (OSCC). Carcinoma-associated fibroblasts (CAFs) may mediate podoplanin expression. However, the role of podoplanin in OSCC cell and fibroblast interaction remains elusive. In the present study, we found that positive podoplanin expression in OSCC cells correlated with smooth muscle actin (α-SMA) expression in CAFs. Using CAFs and normal mucosal fibroblasts (NFs), we established indirect and direct co-culture systems mimicking the structure of OSCC...
April 29, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29707793/interleukin-6-induces-vegf-secretion-from-prostate-cancer-cells-in-a-manner-independent-of-androgen-receptor-activation
#14
Kenichiro Ishii, Takeshi Sasaki, Kazuhiro Iguchi, Shinya Kajiwara, Manabu Kato, Hideki Kanda, Yoshifumi Hirokawa, Kiminobu Arima, Atsushi Mizokami, Yoshiki Sugimura
BACKGROUND: The reduced androgen-sensitivity of prostate cancer (PCa) cells is an important clinical development because of its association with the cells' progression to castration-resistant prostate cancer (CRPC). During androgen deprivation therapy (ADT), stroma-derived growth factors and cytokines can activate the androgen receptor (AR). For example, IL-6 is a multifunctional cytokine that is involved in the malignancy of PCa cells through AR activation. In the present study, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines to investigate the relationship between the responsiveness of PCa cells to IL-6 treatment and the cellular AR signaling pathway...
April 29, 2018: Prostate
https://www.readbyqxmd.com/read/29707149/let-7b-inhibits-cancer-promoting-effects-of-breast-cancer-associated-fibroblasts-through-il-8-repression
#15
Bothina Al-Harbi, Siti-Fauziah Hendrayani, Gabriela Silva, Abdelilah Aboussekhra
Cancer-associated fibroblasts (CAFs) are major players in the development and spread of breast carcinomas through non-cell-autonomous signaling. These paracrine effects are under the control of several genes and microRNAs. We present here clear evidence that let-7b, a tumor suppressor microRNA, plays key roles in the persistent activation of breast stromal fibroblasts and their functional interplay with cancer cells. We have first shown that let-7b is down-regulated in CAFs as compared to their corresponding normal adjacent fibroblasts, and transient specific let-7b inhibition permanently activated breast fibroblasts through induction of the IL-6-related positive feedback loop...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29684209/drug-review-pazopanib
#16
Shingo Miyamoto, Shigenori Kakutani, Yujiro Sato, Akira Hanashi, Yoshitaka Kinoshita, Akira Ishikawa
Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -β, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma...
April 19, 2018: Japanese Journal of Clinical Oncology
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
#17
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/29679033/innovatively-therapeutic-strategy-on-lung-cancer-by-daily-drinking-antioxidative-plasmon-induced-activated-water
#18
Chien-Kai Wang, Hsiao-Chien Chen, Sheng-Uei Fang, Chia-Wen Ho, Cheng-Jeng Tai, Chih-Ping Yang, Yu-Chuan Liu
Many human diseases are inflammation-related, such as cancer and those associated with aging. Previous studies demonstrated that plasmon-induced activated (PIA) water with electron-doping character, created from hot electron transfer via decay of excited Au nanoparticles (NPs) under resonant illumination, owns reduced hydrogen-bonded networks and physchemically antioxidative properties. In this study, it is demonstrated PIA water dramatically induced a major antioxidative Nrf2 gene in human gingival fibroblasts which further confirms its cellular antioxidative and anti-inflammatory properties...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29675784/isolation-of-normal-fibroblasts-and-their-cancer-associated-counterparts-cafs-for-biomedical-research
#19
Barbora Dvořánková, Lukáš Lacina, Karel Smetana
Cancer-associated fibroblasts (CAFs) represent a crucial component of cancer microenvironment. CAFs significantly influence biological properties of various types of cancer in terms of local aggressiveness, recurrence, and metastatic behaviour. This chapter summarizes a simple protocol for isolation of normal fibroblasts and their cancer-associated counterparts from normal human skin and mucosa, respectively, as well as from samples of human tumours such as basal/squamous carcinoma, melanoma, and breast cancer, and employment of this procedure for other types of cancer is possible...
April 20, 2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29671926/cancer-as-a-tissue-the-significance-of-cancer-stromal-interactions-in-the-development-morphogenesis-and-progression-of-human-upper-digestive-tract-cancer
#20
REVIEW
Hiroshi Yokozaki, Yu-Ichiro Koma, Manabu Shigeoka, Mari Nishio
We review the significance of cancer-stromal interactions (CSIs) in the development, morphogenesis and progression of human gastric and esophageal cancer based on the data obtained from co-culture experiments. Orthotopic fibroblasts in the gastric cancer stroma not only promoted their growth by cancer cells but were also responsible for the mobility, morphogenesis and epithelial-to-mesenchymal transition (EMT) of the cancer cells through CSI. Bone marrow-derived mesenchymal stem cells could be part of the origin of cancer-associated fibroblasts (CAFs) of the gastric cancer providing an advantageous microenvironment for the restoration of cancer stem cells with the induction of the EMT...
April 19, 2018: Pathology International
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