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fibroblast cells metastasis

Matthias Müller, Yimin Wang, Michael R Squillante, Kathryn D Held, R Rox Anderson, Martin Purschke
BACKGROUND AND PURPOSE: Radiation therapy is the gold standard treatment for inoperable malignant tumors. However, due to the heterogeneity of the tumor, some regions are more radio resistant and can lead to metastasis and tumor recurrence. In this study, we propose combining traditional X-ray treatment with UVC-emitting LuPO4 :Pr3+ nanoparticles (NPs) to increase the tumor control as well as to reduce tumor recurrence and metastasis. These NPs convert ionizing radiation into UVC-photons (UVC range: 200-280 nm) locally at the tumor site...
December 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Qianqian Wang, Zhuqian Li, Li Sun, Bin Chen, Yuanyuan Zhao, Bo Shen, Miaolin Zhu, Xiangdong Zhao, Changgen Xu, Mei Wang, Wenrong Xu, Wei Zhu
Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been identified to be closely associated with cancer progression. Our previous experimental results showed that BM-MSCs promote tumor growth and metastasis of gastric cancer through paracrine-soluble cytokines or exosomes. However, the elements that affect the role of BM-MSCs in promoting tumor metastasis are not clear. It is known that thrombocytosis in cancer patients is very common. Recently, platelets are recognized to play a critical role in tumor progression...
2018: OncoTargets and Therapy
Shan Wang, Zhiguo Miao, Qiyuan Yang, Yimin Wang, Jinzhou Zhang
Colon cancer is still one of the most common causes of cancer in human and is characterized by lymphocyte infiltrates and originates from the epithelial cells found in the lining of colon or rectum of the gastrointestinal tract. Mesenchymal stem cells (MSCs) are composed of the multipotent stem cell group of stroma and can be differentiated as various cell lineages, such as fibroblasts, osteoblasts, and adipocytes. MSCs provide mechanical and structural support and have potential functions during tumor growth and metastasis...
2018: Canadian Journal of Gastroenterology & Hepatology
Chung-Jung Liu, Yao-Kuang Wang, Fu-Chen Kuo, Wen-Hung Hsu, Fang-Jung Yu, Shuchen Hsieh, Ming-Hong Tai, Deng-Chyang Wu, Chao-Hung Kuo
Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. Helicobacter pylori ( H. pylori ) infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer...
November 30, 2018: Cancers
Rangasudhagar Radhakrishnan, Ji Hee Ha, Muralidharan Jayaraman, Jinsong Liu, Katherine Moxley, Ciro Isidoro, Anil K Sood, Yong Sang Song, Danny N Dhanasekaran
Cancer Associated fibroblasts (CAFs) play a critical role in cancer progression, metastasis, and therapy resistance. Molecular events that confer CAF-phenotype to predecessor-cells are not fully understood. We demonstrate here that the ovarian cancer cell-conditioned medium (OCC-CM) induces CAF-phenotype in MRC5 lung-fibroblasts and it can be mimicked by LPA. While OCC-CM and LPA stimulated the expression of cellular CAF-markers by 3-days, they induced aerobic glycolysis, a metabolic marker for CAF, by 6 hrs...
November 29, 2018: Cancer Letters
Jun Xiao, Jian-Hong Zhong, Sheng-Hong Wei, Zai-Sheng Ye, Fu-Sheng Gong, Chang Wang, Yi Zeng, Lu-Chuan Chen
BACKGROUND: Cancer associated fibroblasts (CAFs) are known to be crucial constituents of cancer microenvironment (CME) and play an important role in initiation, progression and metastasis of various types of cancer, such as oral cancer, pancreatic cancer, and gastric cancer. CAFs are usually derived from normal fibroblasts (NFs), but the mechanism of the transition in gastric cancer has not yet been fully elucidated. METHODS: qRT-PCR and western blot were employed to investigate differences of miR-141 and STAT4 expression respectively...
November 28, 2018: Experimental and Molecular Pathology
Cheng-Yun Pan, Na Xu, Xiao-Li Liu, Xuan Zhou, Yan-Ju Li, Ji-Shi Wang
Cancer-associated fibroblasts (CAF), as one of the most important components of tumor microenvironment, which plays important role in tumorigenesis, development, infiltration and metastasis of cancers. In a variety of solid tumors, CAF can even determine the fate of tumor cells. In view of its pivotal role in promoting tumor progression, CAF has recently become a therapeutic target for a variety of tumors. However, there are a few studies on CAF in hematological malignancies. Recent studies have found that the resistance, relapse of AML, MM, CLL and myelofibrosis of MPN closely relate with CAF, so targeting CAF can effectively enhance the killing effect of chemotherapy drugs on tumor cells, thus improve the efficacy, CAF is expected to become a new target for the treatment of hematological malignancies...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
David Novo, Nikki Heath, Louise Mitchell, Giuseppina Caligiuri, Amanda MacFarlane, Dide Reijmer, Laura Charlton, John Knight, Monika Calka, Ewan McGhee, Emmanuel Dornier, David Sumpton, Susan Mason, Arnaud Echard, Kerstin Klinkert, Judith Secklehner, Flore Kruiswijk, Karen Vousden, Iain R Macpherson, Karen Blyth, Peter Bailey, Huabing Yin, Leo M Carlin, Jennifer Morton, Sara Zanivan, Jim C Norman
Mutant p53s (mutp53) increase cancer invasiveness by upregulating Rab-coupling protein (RCP) and diacylglycerol kinase-α (DGKα)-dependent endosomal recycling. Here we report that mutp53-expressing tumour cells produce exosomes that mediate intercellular transfer of mutp53's invasive/migratory gain-of-function by increasing RCP-dependent integrin recycling in other tumour cells. This process depends on mutp53's ability to control production of the sialomucin, podocalyxin, and activity of the Rab35 GTPase which interacts with podocalyxin to influence its sorting to exosomes...
November 29, 2018: Nature Communications
Zhuo Chen, Lin-Jiang Tong, Bai-You Tang, Hong-Yan Liu, Xin Wang, Tao Zhang, Xian-Wen Cao, Yi Chen, Hong-Lin Li, Xu-Hong Qian, Yu-Fang Xu, Hua Xie, Jian Ding
The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor with an IC50 of 19 nM among a panel of 20 tyrosine kinases. C11 inhibited cell proliferation in various tumors, particularly bladder cancer and breast cancer. C11 also inhibited breast cancer MDA-MB-231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downstream signaling pathway...
November 28, 2018: Acta Pharmacologica Sinica
Guoming Hu, Shimin Wang, Feng Xu, Qiannan Ding, Wei Chen, Kefang Zhong, Liming Huang, Qi Xu
BACKGROUND/AIMS: Tumor-infiltrating fibroblasts are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin+ fibroblasts in human solid tumors still remains controversial. Therefore, we performed the meta-analysis to better understand the role of this subpopulation in prognosis prediction for patients with solid tumor. METHODS: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral podoplanin+ fibroblast density detected by immunohistochemical method and overall survival (OS) and/or disease-free survival (DFS) in patients with solid tumor, then computed extracted data into hazard ratios for OS, DFS and clinicopathological features with STATA 12...
November 26, 2018: Cellular Physiology and Biochemistry
J M Houthuijzen, J Jonkers
Tumor cells exist in close proximity with non-malignant cells. Extensive and multilayered crosstalk between tumor cells and stromal cells tailors the tumor microenvironment (TME) to support survival, growth, and metastasis. Fibroblasts are one of the largest populations of non-malignant host cells that can be found within the TME of breast, pancreatic, and prostate tumors. Substantial scientific evidence has shown that these cancer-associated fibroblasts (CAFs) are not only associated with tumors by proximity but are also actively recruited to developing tumors where they can influence other cells of the TME as well as influencing tumor cell survival and metastasis...
November 21, 2018: Cancer Metastasis Reviews
Mojgan Karimabad Noroozi, Mehdi Mahmoodi, Abdolah Jafarzadeh, Ali Darekordi, Mohamad Reza Hajizadeh, Gholamhossein Hassanshahi
The indole-3-carbinol (I3C) displays anti-proliferative and anti-cancer activities against human cancer cells. Cellular proliferation is an important event associated with cancer development and continued progression. This manifest is described by altered expression and/or functions of cell cycle related proteins. The constitutive activation of many signal transduction pathways also stimulates cell growth. The immediate stages in tumor development are accompanied by a fibrogenic response and the progression of a hypoxic environment, is in favor of the survival and proliferatory functions of cancer stem cells...
November 16, 2018: Mini Reviews in Medicinal Chemistry
Qiqing Sun, Bo Zhang, Qiangsheng Hu, Yi Qin, Wenyan Xu, Wensheng Liu, Xianjun Yu, Jin Xu
Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most challenging lethal tumors and has a very poor prognosis. In addition to cancer cells, the tumor microenvironment created by a repertoire of resident and recruited cells and the extracellular matrix also contribute to the acquisition of hallmarks of cancer. Among these factors, cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment. CAFs originate from the activation of resident fibroblasts and pancreatic stellate cells, the differentiation of bone marrow-derived mesenchymal stem cells and epithelial-to-mesenchymal transition...
2018: Theranostics
Jacqui A McGovern, Abbas Shafiee, Ferdinand Wagner, Christoph A Lahr, Marietta Landgraf, Christoph Meinert, Elizabeth D Williams, Pamela J Russell, Judith A Clements, Daniela Loessner, Boris M Holzapfel, Gail P Risbridger, Dietmar W Hutmacher
The primary tumor microenvironment is inherently important in prostate cancer (PCa) initiation, growth and metastasis. However, most current PCa animal models are based on the injection of cancer cells into the blood circulation and bypass the first steps of the metastatic cascade, hence failing to investigate the influence of the primary tumor microenvironment on PCa metastasis. Here, we investigated the spontaneous metastasis of PC3 human PCa cells from humanized prostate tissue, containing cancer-associated fibroblasts (CAFs) and prostate lymphatic and blood vessel endothelial cells (BVEC), to humanized tissue-engineered bone constructs (hTEBC) in NOD-SCID IL2Rγnull (NSG) mice...
November 13, 2018: Cancers
Akihiko Sakamoto, Shunsuke Kunou, Kazuyuki Shimada, Makoto Tsunoda, Tomohiro Aoki, Chisako Iriyama, Akihiro Tomita, Shigeo Nakamura, Fumihiko Hayakawa, Hitoshi Kiyoi
Cancer-associated fibroblasts (CAFs) are a key component in the tumor microenvironment and play functional roles in tumor metastasis and resistance to chemotherapies. We have previously reported that CAFs isolated from lymphoma samples increase anaerobic glycolysis and decrease intracellular production of reactive oxygen species, promoting the survival of tumor cells. Here, we analyzed the mechanisms underlying this support of tumor-cell survival by CAFs. As direct contact between lymphoma cells and CAFs was not indispensable to survival support, we identified that the humoral factor pyruvate was significantly secreted by CAFs...
November 13, 2018: Cancer Science
Masoud Najafi, Bagher Farhood, Keywan Mortezaee
Cancer stem cells (CSCs) are self-renewable cell types that are identified in most types of liquid and solid cancers and contributed to tumor onset, expansion, resistance, recurrence, and metastasis after therapy. CSCs are identified from the expression of cell surface markers, which is tumor-type dependent. The transition between CSCs with cancer cells and other non-CSCs occurs in cancers, which is possibly under the control of signals from CSCs and tumor microenvironment (TME), including CSC niche. Cancer-associated fibroblasts are among the most influential cells for promoting both differentiation of CSCs and dedifferentiation of non-CSCs toward attaining a CSC-like phenotype...
November 11, 2018: Journal of Cellular Physiology
Xiuying Li, Fengchang Huang, Xiaoyu Xu, Shuenqin Hu
Cancer-associated fibroblasts (CAFs) constitute a major component of the tumor microenvironment. CAFs regulated the growth and development, invasion and metastasis of primary tumors, as well as response to treatment. Recent studies indicated that monoclonal antibody therapies had limited success, thus more effective polyclonal antibodies (Poly Abs) is urgently needed. Poly Abs is a possible alternative because they target multiple antigens simultaneously. In this report, we prepared Poly Abs by immunizing rabbits with the bFGF-activated fibroblasts...
2018: International Journal of Biological Sciences
Prashant V Bommi, Sriram Ravindran, Pradip Raychaudhuri, Srilata Bagchi
DDB2 is a sensor of DNA damage and it plays an important role in Global Genomic Repair (GG-NER). Our previous studies show that DDB2 is involved in the regulation of metastasis in colon adenocarcinoma. Squamous Cell Carcinomas in the Oral/Head & Neck region (HNSCC) are particularly aggressive due to high incidence of recurrence and distant metastasis. In this study, we show that DDB2 expression is downregulated in advanced HNSCCs and loss of DDB2 expression coincides with reduced survival. Recent meta-analysis of gene expression data characterized the mesenchymal-type (EMT-type) as one most aggressive cancer cluster in HNSCC...
October 5, 2018: Oncotarget
Guoming Hu, Feng Xu, Kefang Zhong, Shimin Wang, Liming Huang, Wei Chen
Purpose: Activated tumor-infiltrating fibroblasts were significantly associated with survival of cancer patients. However, they are heterogeneous population, and the prognostic role of these cells in human breast cancer still remains controversial. Herein, we performed the meta-analysis to better understand the role of these cells in prognosis prediction for breast cancer patients. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral activated fibroblast density detected by immunohistochemical (IHC) method and overall survival (OS) and/or disease-free survival (DFS) in breast cancer patients, then computed extracted data into hazard ratios (HRs) for OS, DFS and clinicopathological features such as lymph node metastasis, TNM stage with STATA 12...
2018: Journal of Cancer
Jiaqi Mi, Erika Hooker, Steven Balog, Hong Zeng, Daniel T Johnson, Yongfeng He, Eun-Jeong Yu, Huiqing Wu, Vien Le, Dong-Hoon Lee, Joseph Aldahl, Mark L Gonzalgo, Zijie Sun
Emerging evidence has shown that the hepatocyte growth factor (HGF) and its receptor, MET proto-oncogene, receptor tyrosine kinase (MET), promote cell proliferation, motility, morphogenesis, and angiogenesis. While up-regulation of MET expression has been observed in aggressive and metastatic prostate cancer, a clear understanding of MET function in prostate tumorigenesis remains elusive. Here, we developed a conditional Met transgenic mouse strain, H11Met/+ :PB-Cre4 , to mimic human prostate cancer cells with increased MET expression in the prostatic luminal epithelium...
November 6, 2018: Journal of Biological Chemistry
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