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Carcinoma-Associated Fibroblasts

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https://www.readbyqxmd.com/read/29330502/targeting-insulin-like-growth-factor-i-and-extracellular-matrix-interactions-in-melanoma-progression
#1
Berline Murekatete, Ali Shokoohmand, Jacqui McGovern, Lipsa Mohanty, Christoph Meinert, Brett G Hollier, Alfred Zippelius, Zee Upton, Abhishek S Kashyap
Insulin-like growth factor (IGF)-I binds to the ECM protein vitronectin (VN) through IGF binding proteins (IGFBPs) to enhance proliferation and migration of skin keratinocytes and fibroblasts. Although evidence exists for the role of individual components of the complex (IGF-I, IGFBP-3 and VN), the cellular functions stimulated by these proteins together as a complex remains un-investigated in melanoma cells. We report here that the IGF-I:IGFBP-3:VN trimeric complex stimulates a dose-dependent increase in the proliferation and migration of WM35 and Sk-MEL28 melanoma cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29325547/paracrine-and-epigenetic-control-of-caf-induced-metastasis-the-role-of-hotair-stimulated-by-tgf-%C3%A3-1-secretion
#2
Yu Ren, Huan-Huan Jia, Yi-Qi Xu, Xuan Zhou, Xiao-Hui Zhao, Yun-Fei Wang, Xin Song, Zhi-Yan Zhu, Ting Sun, Yan Dou, Wei-Ping Tian, Xiu-Lan Zhao, Chun-Sheng Kang, Mei Mei
BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines...
January 11, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29321666/are-there-multiple-cells-of-origin-of-merkel-cell-carcinoma
#3
REVIEW
J C Sunshine, N S Jahchan, J Sage, J Choi
Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29312628/mir-520f-promotes-cell-aggressiveness-by-regulating-fibroblast-growth-factor-16-in-hepatocellular-carcinoma
#4
Feng Feng Xu, Wen Feng Xie, Guo Qing Zha, Hong Wu Chen, Liang Deng
Cancer metastasis is a multistep cellular process, which has be confirmed one of mainly causes of cancer associated-death in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in tumorigenesis function as either tumor suppressor genes or oncogenes. In order to elaborate the critical miRNAs and their targets in HCC, we compared the differential expression of miRNA between HCC tissues and normal tissues. Microarray analysis revealed there were several significantly up-expression miRNAs in HCC, compared to normal solid tissue...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29301607/force-mediated-proinvasive-matrix-remodeling-driven-by-tumor-associated-mesenchymal-stem-like-cells-in-glioblastoma
#5
Eun-Jung Lim, Yongjoon Suh, Seungmo Kim, Seok-Gu Kang, Su-Jae Lee
In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling...
January 5, 2018: BMB Reports
https://www.readbyqxmd.com/read/29295532/stromal-expression-of-marcks-protein-in-ovarian-carcinomas-has-unfavorable-prognostic-value
#6
Raoudha Doghri, Maroua Manai, Pascal Finetti, Maha Driss, Emilie Agavnian, Marc Lopez, Meriam Elghardallou, Emmanuelle Charafe-Jauffret, Mohamed Manai, Max Chaffanet, Daniel Birnbaum, Karima Mrad, François Bertucci
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Identification of new therapeutic targets is crucial. MARCKS, myristoylated alanine-rich C-kinase substrate, has been implicated in aggressiveness of several cancers and MARCKS inhibitors are in development. Using immunohistochemistry (IHC), we retrospectively assessed MARCKS expression in epithelial and stromal cells of 118 pre-chemotherapy EOC samples and 40 normal ovarian samples from patients treated at Salah Azaiez Institute. We compared MARCKS expression in normal versus cancer samples, and searched for correlations with clinicopathological features, including overall survival (OS)...
December 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29290975/gper-is-involved-in-the-regulation-of-the-estrogen-metabolizing-cyp1b1-enzyme-in-breast-cancer
#7
Francesca Cirillo, Michele Pellegrino, Rocco Malivindi, Vittoria Rago, Silvia Avino, Luigina Muto, Vincenza Dolce, Adele Vivacqua, Damiano Cosimo Rigiracciolo, Paola De Marco, Anna Sebastiani, Sergio Abonante, Miki Nakajima, Rosamaria Lappano, Marcello Maggiolini
The cytochrome P450 1B1 (CYP1B1) is a heme-thiolate monooxygenase involved in both estrogen biosynthesis and metabolism. For instance, CYP1B1 catalyzes the hydroxylation of E2 leading to the production of 4-hydroxyestradiol that may act as a potent carcinogenic agent. In addition, CYP1B1 is overexpressed in different tumors including breast cancer. In this scenario, it is worth mentioning that CYP1B1 expression is triggered by estrogens through the estrogen receptor (ER)α in breast cancer cells. In the present study, we evaluated whether the G protein estrogen receptor namely GPER may provide an alternate route toward the expression and function of CYP1B1 in ER-negative breast cancer cells, in main players of the tumor microenvironment as cancer associated fibroblasts (CAFs) that were obtained from breast cancer patients, in CAFs derived from a cutaneous metastasis of an invasive mammary ductal carcinoma and in breast tumor xenografts...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273462/fibroblast-activation-proteins-%C3%AE-suppress-tumor-immunity-by-regulating-t-cells-and-tumor-associated-macrophages
#8
Chun Mei Hou, Xue Mei Qu, Jian Zhang, Ting Ting Ding, Wei Han, Guang Chuan Ji, Zhao Hua Zhong, He Chen, Feng-Min Zhang
Fibroblast activation protein-α (FAPα) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in >90% of malignant epithelial carcinomas. FAPα regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment...
December 19, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29259267/dysregulation-of-mir-196b-in-head-and-neck-cancers-leads-to-pleiotropic-effects-in-the-tumor-cells-and-surrounding-stromal-fibroblasts
#9
Saúl Álvarez-Teijeiro, Sofía T Menéndez, M Ángeles Villaronga, Juan P Rodrigo, Lorea Manterola, Lucas de Villalaín, Juan C de Vicente, Laura Alonso-Durán, M Pilar Fernández, Charles H Lawrie, Juana M García-Pedrero
The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (HNSCC), and also the impact on the surrounding tumor microenvironment. Increased miR-196b levels were detected in 95% of primary tumors and precancerous lesions, although no significant differences were observed between non-progressing versus progressing dysplasias...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29259010/lsd1-stimulates-cancer-associated-fibrobasts-to-drive-notch3-dependent-self-renewal-of-liver-cancer-stem-like-cells
#10
Chungang Liu, Limei Liu, Xuejiao Chen, Jiamin Cheng, Heng Zhang, Chengcheng Zhang, Juanjuan Shan, Junjie Shen, Cheng Qian
Cancer stem-like cells (CSC) in hepatocellular carcinoma (HCC) are thought to mediate therapeutic resistance and poor survival outcomes, but their intrinsic and extrinsic control is not well understood. In this study, we found that the chromatin modification factor LSD1 is highly expressed in HCC CSC where it decreases during differentiation. LSD1 was responsible for maintaining CSC self-renewal and tumorigenicity in HCC and its overexpression was sufficient to drive self-renewal of non-CSC.Levels of acetylated LSD1 were low in CSC with high LSD1 activity, and these CSC were capable of self-renewal...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29250193/role-of-ccl20-ccr6-and-the-erk-signaling-pathway-in-lung-adenocarcinoma
#11
Xiao-Peng Zhang, Zhi-Juan Hu, Ai-Hong Meng, Guo-Chen Duan, Qing-Tao Zhao, Jing Yang
Previous studies have revealed that carcinoma-associated fibroblasts communicate microenvironment-derived signals through chemokine/chemokine receptor interaction, resulting in carcinogenesis. C-C motif chemokine ligand 20 (CCL20)/C-C motif chemokine receptor 6 (CCR6) interactions are involved in the pathogenesis of colonic malignancies. The present study aimed to characterize the roles of CCL20/CCR6 and the extracellular signal-regulated kinase (ERK) signaling pathway in lung adenocarcinoma growth. Lung adenocarcinoma samples obtained at surgery were assessed for the expression, tissue localization and production of CCL20/CCR6...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29248714/foxq1-ndrg1-axis-exacerbates-hepatocellular-carcinoma-initiation-via-enhancing-crosstalk-between-fibroblasts-and-tumor-cells
#12
Qin Luo, Chao-Qun Wang, Lu-Yu Yang, Xiao-Mei Gao, Hao-Ting Sun, Yu Zhang, Kai-Li Zhang, Ying Zhu, Yan Zheng, Yuan-Yuan Sheng, Lu Lu, Hu-Liang Jia, Wen-Qiang Yu, Jie Liu, Qiong-Zhu Dong, Lun-Xiu Qin
Cancer associated fibroblast (CAF) is a well-known microenvironment contributor for the development of hepatocellular carcinoma (HCC), while forkhead box proteins are also critical to exacerbate HCC malignancy. However, whether FOX proteins are involved in the crosstalk between CAFs and HCC cells remains unclear. In the present study, we reveal that CAFs induce forkhead box Q1 (FOXQ1) expression, and N-myc downstream-regulated gene 1 (NDRG1) is therefore trans-activated to enhance HCC initiation. Intriguingly, pSTAT6/C-C motif chemokine ligand 26 (CCL26) signaling is induced by FOXQ1/NDRG1 axis, thus recruiting hepatic stellate cells (HSCs), the main cellular source of CAFs, to the tumor microenvironment...
December 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29246104/mechanically-tuned-3-dimensional-hydrogels-support-human-mammary-fibroblast-growth-and-viability
#13
Kathryn Woods, Catlyn Thigpen, Jennifer Peyling Wang, Hana Park, Abigail Hielscher
BACKGROUND: Carcinoma associated fibroblasts (CAFs or myofibroblasts) are activated fibroblasts which participate in breast tumor growth, angiogenesis, invasion, metastasis and therapy resistance. As such, recent efforts have been directed toward understanding the factors responsible for activation of the phenotype. In this study, we have investigated how changes in the mechanical stiffness of a 3D hydrogel alter the behavior and myofibroblast-like properties of human mammary fibroblasts (HMFs)...
December 16, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29242607/the-impact-of-stromal-hic-5-on-the-tumorigenesis-of-colorectal-cancer-through-lysyl-oxidase-induction-and-stromal-remodeling
#14
Tomokatsu Omoto, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Akira Orimo, Koji Ohnishi, Kosuke Yoshihara, Aya Miyauchi, Shuo Li, Lin Gao, Takahiro Umemoto, Junichi Tanaka, Kenta Nakahara, Motohiro Takeya, Fumio Ishida, Shin-Ei Kudo, Shogo Haraguchi, Takuro Miyazaki, Akira Miyazaki
Carcinoma-associated fibroblasts (CAFs) influence tumor initiation, progression, and metastasis within the tumor-associated stroma. This suggests that CAFs would be a potential target for tumor therapy. Here we found that Hydrogen peroxide-inducible clone-5 (Hic-5), also named transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was strongly induced in CAFs found in human colorectal cancer. To investigate the role of Hic-5 in CAFs, we isolated CAFs and the control counterpart normal fibroblasts (NFs) from human colorectal cancer and non-cancerous regions, respectively...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29228606/identifying-tumor-promoting-genomic-alterations-in-tumor-associated-fibroblasts-via-retrovirus-insertional-mutagenesis
#15
Lijie Rong, Yangyang Bian, Shubai Liu, Xiaoman Liu, Xiao Li, Haiyang Liu, Jinxue Zhou, Jirun Peng, Henghui Zhang, Hongsong Chen, Zhihai Qin
Tumor-associated fibroblasts (TAFs) are often essential for solid tumor growth. However, few genetic or epigenetic alterations have been found in TAFs during the progression of solid tumors. Employing a tumor-stromal cell co-injection model, we adapted here retroviral-insertional mutagenesis to stromal cells to identify novel tumor-associated genes in TAFs. We successfully identified 20 gene candidates that might modulate tumor growth if altered in TAFs at genomic level. To validate our finding, the function of one of the candidate genes, tubulin tyrosine ligase (Ttl), was further studied in TAFs from fibrosarcoma, colon, breast and hepatocarcinoma...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221201/functional-fgfr4-gly388arg-polymorphism-contributes-to-oral-squamous-cell-carcinoma-susceptibility
#16
Chia-Hsuan Chou, Ming-Ju Hsieh, Chun-Yi Chuang, Jen-Tsun Lin, Chia-Ming Yeh, Pao-Yu Tseng, Shun-Fa Yang, Mu-Kuan Chen, Chiao-Wen Lin
Aberrations of the fibroblast growth factor receptor 4 (FGFR4) genomic region include amplification of FGFR4, activation of FGFR4 kinase domain mutations, and overexpression of FGFR4, which lead to sustained cell proliferation and contribute to tumor development. However, the association between FGFR4 single-nucleotide polymorphisms (SNPs) and risk of oral squamous cell carcinoma (OSCC) remains to be determined. We investigated the relationships between FGFR4 genetic polymorphisms, OSCC development and clinicopathological variables...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210650/reprograming-carcinoma-associated-fibroblasts-by-micrornas
#17
Y Xu, X Zhou, M Mei, Y Ren
Carcinoma-associated fibroblasts (CAFs) are activated fibroblasts during development of several cancer types, and therefore emerge as an attractive therapeutic target for cancer therapy. Drugs such as PT-100 and sibrotuzumab that block the functions of CAFs have already been in clinical trials. However, these drugs exhibit limited efficacy in patients, partially due to the fact that currently used biomarkers for determining efficacy are not CAF-specific. Furthermore, depletion of CAFs may promote carcinogenesis and accelerate cancer progression by inducing immunosuppression and hypoxia, leading to reduced survival...
December 4, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29207019/stromal-epithelial-lactate-shuttle-induced-by-tumor%C3%A2-derived-interleukin%C3%A2-1%C3%AE-promotes-cell-proliferation-in-oral-squamous-cell-carcinoma
#18
Jie Wu, Yun Hong, Tong Wu, Juan Wang, Xiaobing Chen, Zhi Wang, Bin Cheng, Juan Xia
Stromal-epithelial lactate shuttle is an essential process to support fast‑growing tumor cells, however, the underlying mechanism remains ambiguous. Interleukin‑1β (IL‑1β), which is a key node gene in both stromal and epithelial cells of oral squamous cell carcinoma (OSCC), may participate in this metabolic reprogramming. In the present study, anaerobic glycolysis of cancer‑associated fibroblasts (CAFs) was evaluated and the role of IL‑1β in regulating stromal‑epithelial lactate shuttle was determined...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29199004/dicer-reprograms-stromal-fibroblasts-to-a-pro-inflammatory-and-tumor-promoting-phenotype-in-ovarian-cancer
#19
Zongyuan Yang, Ping Jin, Sen Xu, Taoran Zhang, Xin Yang, Xiaoting Li, Xiao Wei, Chaoyang Sun, Gang Chen, Ding Ma, Qinglei Gao
Inflammation and host stromal activation contribute significantly to ovarian cancer (OC) initiation and malignant progression. However, the complex reciprocal interactions between them are largely unknown. Here, we discovered that the tumor suppressor gene Dicer was paradoxically overexpressed in ovarian tumor stroma, and induced fibroblast activation and stromal inflammation. Dicer transformed normal fibroblasts to a carcinoma-associated fibroblast (CAF)-like state, which was morphologically spread out and functionally activated to fuel tumor invasion and metastasis...
November 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29184085/diverse-changes-of-circulating-fibroblast-growth-factor-21-levels-in-hepatitis-b-virus-related-diseases
#20
Liang Wu, Qingchun Pan, Guangyu Wu, Lingling Qian, Jing Zhang, Lei Zhang, Qichen Fang, Guoqing Zang, Yudong Wang, George Lau, Huating Li, Weiping Jia
Fibroblast growth factor 21 (FGF21), a stress-induced hormone in the liver, has been shown the protective functions in pathological conditions. The study investigated the association of circulating FGF21 with hepatitis B virus (HBV) infection and its related diseases. Serum FGF21 levels were measured in 33 acute hepatitis B (AHB), 75 chronic hepatitis B (CHB) and 66 CHB patients with advanced liver diseases including liver cirrhosis, acute-on-chronic liver failure (ALCF) and hepatocellular carcinoma (HCC) together with 200 age- and BMI-matched healthy controls...
November 28, 2017: Scientific Reports
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