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Carcinoma-Associated Fibroblasts

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https://www.readbyqxmd.com/read/28077301/mir-124-down-regulation-is-critical-for-cancer-associated-fibroblasts-enhanced-tumor-growth-of-oral-carcinoma
#1
Xia Li, Qinqiao Fan, Jinyun Li, Jing Song, Yangcong Gu
Cancer associated fibroblasts (CAFs) are known to be involved in initiation, progression and metastasis of various cancers. However, the molecular mechanism of how CAFs affects the biological function of oral cancer (OC) has not been fully-addressed. In this study, we demonstrated that miR-124 was downregulated in oral CAFs and oral cancer cells (OCCs) when compared with matched normal fibroblasts (NFs). Hypermethylation in the promoter region of miR-124 genes was accounted for its downregulation. Interestingly, CAFs but not NFs exerted promotion effect on OCCs cell proliferation, migration and tumor growth in CAFs/NFs-OCCs co-culture...
January 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28070642/distinct-expression-profile-of-stem-cell-markers-lgr5-and-lgr6-in-basaloid-skin-tumors
#2
Bo Gun Jang, Cheol Lee, Hye Sung Kim, Myung Soo Shin, Min Seok Cheon, Jae Wang Kim, Woo Ho Kim
Mammalian epidermis, which is composed of hair follicles, sebaceous glands, and interfollicular epidermis, is maintained by discrete stem cells. In vivo lineage tracing demonstrated that murine LGR5 cells are mainly responsible for hair follicle regeneration whereas LGR6 cells generate sebaceous glands and interfollicular epidermis. However, little is known about their expression in the human skin tumors. In this study, we investigated the expression profile of LGR5 and LGR6 in a variety of human skin tumors including basaloid tumors with follicular differentiation (94 basal cell carcinomas, 18 trichoepitheliomas, 3 basaloid follicular hamartomas, and 12 pilomatricomas) and tumors with ductal differentiation (7 eccrine poromas, 8 hidradenomas, and 5 spiradenomas)...
January 9, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28069043/fgf19-fgfr4-signaling-contributes-to-the-resistance-of-hepatocellular-carcinoma-to-sorafenib
#3
Lixia Gao, Xuli Wang, Yaoliang Tang, Shuang Huang, Chien-An Andy Hu, Yong Teng
BACKGROUND: Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to sorafenib therapy. METHODS: FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28060811/stromal-fibroblasts-from-the-interface-zone-of-triple-negative-breast-carcinomas-induced-epithelial-mesenchymal-transition-and-its-inhibition-by-emodin
#4
Hsiang-Chi Hsu, Liang-Chih Liu, Hao-Yu Wang, Chao-Ming Hung, Ying-Chao Lin, Chi-Tang Ho, Tzong-Der Way
"Triple negative breast cancer" (TNBC) is associated with a higher rate and earlier time of recurrence and worse prognosis after recurrence. In this study, we aimed to examine the crosstalk between fibroblasts and TNBC cells. The fibroblasts were isolated from TNBC patients' tissue in tumor burden zones, distal normal zones and interface zones. The fibroblasts were indicated as cancer-associated fibroblasts (CAFs), normal zone fibroblasts (NFs) and interface zone fibroblasts (INFs). Our study found that INFs grew significantly faster than NFs and CAFs in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28056302/-expression-of-cd10-in-cancer-associated-fibroblasts-and-its-effect-on-initiation-and-progression-of-colorectal-carcinoma
#5
Y Zhu, J J Zheng, F Yang, Q Q Nie, Z L Zhu, H Deng
Objective: To study CD10 expression in cancer-associated fibroblasts (CAF) and related effect on colorectal cancer initiation and progression. Methods: A total of 226 surgical removed colorectal cancer specimens were collected with patient follow-up data. A panel of immunohistochemical markers(CD10, Ki-67, p53, cyclin D1 and β-catenin) were evaluated in carcinomas, adjacent adenomas and paired normal colorectal mucosa with correlation of clinicopathological parameters. Results: CD10 expression was not detected in the normal colorectal mucosa by immunohistochemistry...
December 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28052009/cancer-associated-fibroblasts-promote-an-immunosuppressive-microenvironment-through-the-induction-and-accumulation-of-protumoral-macrophages
#6
Hideyuki Takahashi, Koichi Sakakura, Takeshi Kudo, Minoru Toyoda, Kyoichi Kaira, Tetsunari Oyama, Kazuaki Chikamatsu
Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027646/protein-nanocage-mediated-fibroblast-activation-protein-targeted-photoimmunotherapy-to-enhance-cytotoxic-t-cell-infiltration-and-tumor-control
#7
Zipeng Zhen, Wei Tang, Mengzhe Wang, Shiyi Zhou, Hui Wang, Zhanhong Wu, Zhonglin Hao, Zibo Li, Lin Liu, Jin Xie
Carcinoma-associated fibroblasts (CAFs) are found in many types of cancer and play an important role in tumor growth and metastasis. Fibroblast-activation protein (FAP), which is overexpressed on the surface of CAFs, has been proposed as a universal tumor targeting antigen. However, recent studies show that FAP is also expressed on multipotent bone marrow stem cells. A systematic anti-FAP therapy may lead to severe side effects and even death. Hence, there is an urgent need of a therapy that can selectively kill CAFs without causing systemic toxicity...
January 4, 2017: Nano Letters
https://www.readbyqxmd.com/read/28011493/podoplanin-expression-in-cancer-associated-fibroblasts-predicts-poor-prognosis-in-patients-with-squamous-cell-carcinoma-of-the-lung
#8
Yohei Yurugi, Makoto Wakahara, Yuki Matsuoka, Tomohiko Sakabe, Yasuaki Kubouchi, Tomohiro Haruki, Kanae Nosaka, Ken Miwa, Kunio Araki, Yuji Taniguchi, Tatsushi Shiomi, Hiroshige Nakamura, Yoshihisa Umekita
BACKGROUND/AIM: Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs. PATIENTS AND METHODS: Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/28010894/metabolic-hijacking-a-survival-strategy-cancer-cells-exploit
#9
REVIEW
Megan I Mitchell, Anna-Mart Engelbrecht
The majority of human tumours are comprised of cancerous epithelial cells that coexist with a multitude of different cell types and extracellular matrix components creating the cancer microenvironment. Cancer-associated fibroblasts (CAFs) are the most abundant mesenchymal cell types present within most human carcinomas. Recent evidence suggests that nutrient deprived epithelial cancer cells are able to survive these conditions, as a result of their ability to undergo extensive metabolic reprogramming and exploit the metabolic capacities of surrounding CAFs...
January 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28007785/p38mapk-builds-a-hyaluronan-cancer-niche-to-drive-lung-tumorigenesis
#10
Anna Brichkina, Thomas Bertero, Hui Mun Loh, Nguyet Thi Minh Nguyen, Alexander Emelyanov, Sidwell Rigade, Marius Ilie, Paul Hofman, Cedric Gaggioli, Dmitry V Bulavin
Expansion of neoplastic lesions generates the initial signal that instigates the creation of a tumor niche. Nontransformed cell types within the microenvironment continuously coevolve with tumor cells to promote tumorigenesis. Here, we identify p38MAPK as a key component of human lung cancer, and specifically stromal interactomes, which provides an early, protumorigenic signal in the tissue microenvironment. We found that lung cancer growth depends on short-distance cues produced by the cancer niche in a p38-dependent manner...
December 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/28004985/cyclophosphamide-enhances-anti-tumor-effects-of-a-fibroblast-activation-protein-%C3%AE-based-dna-vaccine-in-tumor-bearing-mice-with-murine-breast-carcinoma
#11
Qiu Xia, Fei Geng, Fang-Fang Zhang, Chen-Lu Liu, Ping Xu, Zhen-Zhen Lu, Yu Xie, Bo Sun, Hui Wu, Bin Yu, Wei Kong, Xiang-Hui Yu, Hai-Hong Zhang
Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other chemotherapy drugs in the treatment of various types of cancer. It can be used not only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10 expression and T regulatory cells (Tregs). Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts in the tumor microenvironment. Immunotherapy based on FAPα, as a tumor stromal antigen, typically induces specific immune response targeting the tumor microenvironment...
December 22, 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27998871/-expressions-of-cyclooxygenase-2-and-basic-fibroblast-growth-factor-in-nasopharyngeal-carcinoma-and-their-association-with-radiotherapy-sensitivity
#12
Jian-Fu Zhao, Meng Xu, Wen-Hui Chen, Feng-Zhi Zhao, Yi-Ming Wang, Cheng-Hai Zhuang
OBJECTIVE: To detect the expressions of cyclooxygenase-2 (COX-2) and basic fibroblast growth factor (bFGF) and evaluate their value in predicting the radiotherapy sensitivity in nasopharyngeal carcinoma (NPC). METHODS: The expressions of COX-2 and bFGF were detected immunohistochemically in biopsy samples of NPC, and their relationship with the radiotherapy sensitivity of the tumors were analyzed. RESULTS: In 97 NPC cases, the positivity rates of COX-2 and bFGF were 71...
December 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27996035/induction-of-cancer-associated-fibroblast-like-cells-by-carbon-nanotubes-dictates-its-tumorigenicity
#13
Sudjit Luanpitpong, Liying Wang, Vincent Castranova, Cerasela Zoica Dinu, Surapol Issaragrisil, Yi Charlie Chen, Yon Rojanasakul
Tumor microenvironment has been recognized as a key determinant of tumor formation and metastasis, but how tumor microenvironment is affected by nanomaterials is essentially unknown. Here, we investigated whether carbon nanotubes (CNTs), a widely used nanomaterial with known carcinogenic potential, can affect cancer-associated fibroblasts (CAFs), which are a key component of tumor microenvironment that provides necessary support for tumor growth. We show for the first time that single-walled CNT and to a lesser extent multi-walled and its COOH-functionalized form induced CAF-like cells, which are non-tumorigenic in animals, but promote tumor growth of human lung carcinoma and CNT-transformed lung epithelial cells...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27959632/the-role-of-cancer-associated-fibroblasts-and-fibrosis-in-liver-cancer
#14
Silvia Affo, Lexing Yu, Robert F Schwabe
Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver...
December 5, 2016: Annual Review of Pathology
https://www.readbyqxmd.com/read/27956804/prognostic-implications-of-fgfr1-and-myc-status-in-esophageal-squamous-cell-carcinoma
#15
Dohee Kwon, Ji Yun Yun, Bhumsuk Keam, Young Tae Kim, Yoon Kyung Jeon
AIM: To investigate the clinicopathological features and prognostic implications of combined MYC and fibroblast growth factor receptor 1 (FGFR1) status in esophageal squamous cell carcinomas (ESCCs). METHODS: All patients with ESCC (n = 180) underwent surgical resection at Seoul National University Hospital sometime between 2000 and 2013. A tissue microarray was constructed using cores obtained from representative tumor areas of formalin-fixed, paraffin-embedded tissue blocks...
November 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27935821/stromal-hedgehog-signaling-maintains-smooth-muscle-and-hampers-micro-invasive-prostate-cancer
#16
Zhaohui Yang, Yu-Ching Peng, Anuradha Gopalan, Dong Gao, Yu Chen, Alexandra L Joyner
It is widely appreciated that reactive stroma or carcinoma-associated fibroblasts can influence epithelial tumor progression. In prostate cancer (PCa), the second most common male malignancy worldwide, the amount of reactive stroma is variable and has predictive value for tumor recurrence. By analyzing human PCa protein and RNA expression databases, we found smooth muscle cells (SMCs) are decreased in advanced tumors, whereas fibroblasts are maintained. In three mouse models of PCa, PB-MYC, ERG/PTEN and TRAMP, we found the composition of the stroma is distinct...
January 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27933957/synthesis-and-antiviral-evaluation-of-octadecyloxyethyl-benzyl-9-2-phosphonomethoxy-ethyl-guanine-ode-bn-pmeg-a-potent-inhibitor-of-transient-hpv-dna-amplification
#17
James R Beadle, Nadejda Valiaeva, Guang Yang, Jei-Hwa Yu, Thomas R Broker, Kathy A Aldern, Emma A Harden, Kathy A Keith, Mark N Prichard, Tracy Hartman, Robert W Buckheit, Louise T Chow, Karl Y Hostetler
Human papillomavirus (HPV) high-risk genotypes such as HPV-16 and HPV-18 cause the majority of anogenital tract carcinomas, including cervical cancer, the second most common malignancy in women worldwide. Currently there are no approved antiviral agents that reduce or eliminate HPV and reverse virus-associated pathology. We synthesized and evaluated several alkoxyalkyl acyclic nucleoside phosphonate diesters and identified octadecyloxyethyl benzyl 9-[(2-phosphonomethoxy)ethyl]guanine (ODE-Bn-PMEG) as an active compound which strongly inhibited transient amplification of HPV-11, -16, and -18 origin-containing plasmid DNA in transfected cells at concentrations well below its cytotoxic concentrations...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27931212/pdgf-aa-mediates-mesenchymal-stromal-cell-chemotaxis-to-the-head-and-neck-squamous-cell-carcinoma-tumor-microenvironment
#18
Tammara L Watts, Ruwen Cui, Peter Szaniszlo, Vicente A Resto, Don W Powell, Irina V Pinchuk
BACKGROUND: The robust desmoplasia associated with head and neck squamous cell carcinoma (HNSCC) suggests that the tumor microenvironment may be an important component in the pathophysiology of this cancer. Moreover, the high recurrence rate and poor clinical response to chemotherapy and radiation treatment further underscores that the non-cancerous cells of the microenvironment, such as mesenchymal stromal cells (MSCs), cancer associated fibroblasts (CAFs), and pericytes, may be important in the pathophysiology of HNSCC...
December 8, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27918691/podoplanin-expression-in-canine-melanoma
#19
Satoshi Ogasawara, Ryusuke Honma, Mika K Kaneko, Yuki Fujii, Yumiko Kagawa, Satoru Konnai, Yukinari Kato
A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues...
December 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27916281/intratumoral-heterogeneity-of-macrophages-and-fibroblasts-in-breast-cancer-is-associated-with-the-morphological-diversity-of-tumor-cells-and-contributes-to-lymph-node-metastasis
#20
Lubov A Tashireva, Evgeny V Denisov, Tatiana S Gerashchenko, Daria N Pautova, Mikhail A Buldakov, Marina V Zavyalova, Julia Kzhyshkowska, Nadezhda V Cherdyntseva, Vladimir M Perelmuter
Recent studies have highlighted the heterogeneity of the tumor microenvironment (ME) and the importance of its analysis to the understanding of its impact on clinical outcomes. In this study, we aimed to analyze the intratumoral distribution of macrophages and fibroblasts in breast cancer (BC) based on the morphological diversity of tumor cells (tubular, alveolar, solid, trabecular and discrete structures) and the clinicopathological parameters of the disease. Thirty-six patients with invasive breast carcinoma of no special type were included in the study...
November 27, 2016: Immunobiology
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