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tumor microenvironment

Nancy Chan, Amy Willis, Naomi Kornhauser, Maureen M Ward, Sharrell B Lee, Eleni Nackos, Bo Ri Seo, Ellen Chuang, Tessa Cigler, Anne Moore, Diana Donovan, Marta Vallee Cobham, Veronica Fitzpatrick, Sarah Schneider, Alysia Wiener, Jessica Guillaume-Abraham, Elnaz Anjom, Richard Zelkowitz, J David Warren, Maureen E Lane, Claudia Fischbach, Vivek Mittal, Linda Vahdat
PURPOSE: Bone marrow derived progenitor cells; including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways model the tumor microenvironment. We hypothesized that copper depletion (CD) using tetrathiomolybdate (TM) would reduce EPCs in high risk for relapse breast cancer (BC) patients (pts). We investigated the effect of TM on the tumor microenvironment in preclinical models. EXPERIMENTAL DESIGN: Stage 2 triple negative BC (TNBC), Stage 3 and stage 4 without any evidence of disease, (NED) BC pts, received oral TM to maintain ceruloplasmin (Cp) between 8-17mg/dL for 2 years or until relapse...
October 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
: The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
October 18, 2016: Acta Biomaterialia
Lan Wei, Kuangfa Li, Xueli Pang, Bianqin Guo, Min Su, Yunxiu Huang, Nian Wang, Feihu Ji, Changli Zhong, Junhong Yang, Zhiqian Zhang, Yulin Jiang, Yifeng Liu, Tingmei Chen
BACKGROUND: Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates the migration of breast cancer cells and angiogenesis, and is also involved in EMT. However, the potential mechanism remains unknown. This study aims to explore the effect of leptin on EMT in breast cancer cells and the underlying mechanism. METHODS: With the assessment of EMT-associated marker expression in MCF-7, SK-BR-3, and MDA-MB-468 cells, the effect of leptin on breast cancer cells was analyzed...
October 21, 2016: Journal of Experimental & Clinical Cancer Research: CR
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
Guosheng Song, Chenghong Ji, Chao Liang, Xuejiao Song, Xuan Yi, Ziliang Dong, Kai Yang, Zhuang Liu
Cancer radiotherapy (RT) is a clinically used tumor treatment strategy applicable for a wide range of solid tumors. However, during RT treatment of tumors, only a small portion of applied ionizing irradiation energy is absorbed by the tumor, in which the largely hypoxic microenvironment also limits the anti-tumor efficacy of RT. In this work, we rationally fabricate polyethylene glycol (PEG) stabilized perfluorocarbon (PFC) nano-droplets decorated with TaOx nanoparticles (TaOx@PFC-PEG) as a multifunctional RT sensitizer...
October 11, 2016: Biomaterials
Seul-Gi Oh, Xian Li, Ho Won Lee, Thoudam Debraj Singh, Sang Bong Lee, Hyun Dong Ji, GhilSuk Yoon, Sung Jin Cho, In-Kyu Lee, Shin Young Jeong, Byeong-Cheol Ahn, Jaetae Lee, Hyeun Wook Chang, Sang-Woo Lee, Yong Hyun Jeon
The inability to monitor the in vivo dynamics of mast cells (MCs) limits the better understanding of its role in cancer progression. Here, we report on noninvasive imaging of MC migration to tumor lesions in mice and evaluation of the effects of migrated MCs on tumor progression through reporter gene-based in vivo optical imaging and glucose metabolism monitoring in cancer with (18)F-fluorodeoxyglucose ((18)F-FDG) in vitro and in vivo. Murine MCs (MC-9) and Lewis lung cancer cells (LLC) expressing an enhanced firefly luciferase (effluc) gene were established, termed MC-9/effluc and LLC/effluc, respectively...
October 13, 2016: Biomaterials
Yi Wang, Yao-Xin Lin, Sheng-Lin Qiao, Hong-Wei An, Yang Ma, Zeng-Ying Qiao, R P Yeshan J Rajapaksha, Hao Wang
Immunotherapy has shown a promising effect for a variety of cancers. However, the immune treatment efficiency of solid tumor is limited due to barely infiltration of immune cells in solid tumor. Researchers realized conversion of tumor supportive macrophages to tumor against ones was an effective method to induce the functional reverse of macrophage and contributed to the subsequent antitumor response. The current challenge in the field is that while making use of cytokines usually coupled with poor-distribution and systemic side effects...
October 4, 2016: Biomaterials
Avishai Shemesh, Aleksandra Kugel, Naama Steiner, Michal Yezersky, Dan Tirosh, Avishay Edri, Omri Teltsh, Benyamin Rosental, Eyal Sheiner, Eitan Rubin, Kerry S Campbell, Angel Porgador
NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-β, IL-15 and IL-18 are able to influence both NKp44 and NKp30 splice variant profiles, leading to cytokine-associated profiles. Placenta and cancerous tissues have many similarities; both are immunologically privileged sites and both share immune tolerance mechanisms to support tissue development. Therefore, we studied the profiles of NKp44 and NKp30 splice variants in these states by comparing (i) decidua from pregnancy disorder and healthy gestation and (ii) matched normal and cancer tissue...
September 27, 2016: Oncotarget
Yu Jin Lee, Kyeong Jin Shin, Soo-Ah Park, Kyeong Su Park, Seorim Park, Kyun Heo, Young-Kyo Seo, Dong-Young Noh, Sung Ho Ryu, Pann-Ghill Suh
G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo...
September 27, 2016: Oncotarget
Lauren S Sherman, Maran Shaker, Veronica Mariotti, Pranela Rameshwar
Mesenchymal stromal/stem cells (MSC) have emerged as a class of cells suitable for cellular delivery of nanoparticles, drugs and micro-RNA cargo for targeted treatments such as tumor and other protective mechanisms. The special properties of MSC underscore the current use for various clinical applications. Examples of applications include but are not limited to regenerative medicine, immune disorders and anti-cancer therapies. In recent years, there has been intense research in modifying MSC to achieve targeted and efficient clinical outcomes...
October 17, 2016: Cytotherapy
Etienne Becht, Nicolas A Giraldo, Laetitia Lacroix, Bénédicte Buttard, Nabila Elarouci, Florent Petitprez, Janick Selves, Pierre Laurent-Puig, Catherine Sautès-Fridman, Wolf H Fridman, Aurélien de Reyniès
We introduce the Microenvironment Cell Populations-counter (MCP-counter) method, which allows the robust quantification of the absolute abundance of eight immune and two stromal cell populations in heterogeneous tissues from transcriptomic data. We present in vitro mRNA mixture and ex vivo immunohistochemical data that quantitatively support the validity of our method's estimates. Additionally, we demonstrate that MCP-counter overcomes several limitations or weaknesses of previously proposed computational approaches...
October 20, 2016: Genome Biology
Naoshi Nishida, Masatoshi Kudo
Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of patients with advanced stage of disease remains unfavorable. Several immune therapies have been applied to HCC, and their responses have not been satisfactory. The immune response to cancer is determined by the balance between the antigenicity of the tumor and the microenvironment of cancer tissues. Generally, accumulated genetic mutations are observed in HCC, which may lead to increased neoantigens on cancer cells with high antigenicity...
October 21, 2016: Oncology
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Tong Zhou, Luke Erber, Bing Liu, Yankun Gao, Hai-Bin Ruan, Yue Chen
Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs...
October 13, 2016: Oncotarget
Yang Yu, Qingyun Zhang, Qinggui Meng, Chen Zong, Lei Liang, Xue Yang, Rui Lin, Yan Liu, Yang Zhou, Hongxiang Zhang, Xiaojuan Hou, Zhipeng Han, Jiwen Cheng
Prostate cancer (PCa) has become the second leading cause of male cancer-related mortality in the United States. Mesenchymal stem cells (MSCs) are able to migrate to tumor tissues, and are thus considered to be novel antitumor carriers. However, due to their immunosuppressive nature, the application of MSCs in PCa therapy remains limited. In this study, we investigated the effect of MSCs overexpressing an NAD-dependent deacetylase sirtuin 1 (MSCs-Sirt1) on prostate tumor growth, and we analyzed the underlying mechanisms...
October 18, 2016: Oncotarget
Vincent Le Coz, Chaobin Zhu, Aurore Devocelle, Aimé Vazquez, Claude Boucheix, Sandy Azzi, Cindy Gallerne, Pierre Eid, Séverine Lecourt, Julien Giron-Michel
Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments. One factor produced by melanoma cells and their microenvironment, insulin-like growth factor-1 (IGF- 1), is linked to epithelial-mesenchymal transition (EMT) and stemness features in several cancers...
October 18, 2016: Oncotarget
Suély V Silva, Maíra A Lima, Nathalie Cella, Ruy G Jaeger, Vanessa M Freitas
Proteins secreted in the extracellular matrix microenvironment (ECM) by tumor cells are involved in cell adhesion, motility, intercellular communication and invasion. The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-ECM interactions and in the generation of new signals from the cell surface. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family have been implicated in tissue remodeling events observed in cancer development, growth and progression...
2016: PloS One
O Lidický, M Šírová, T Etrych
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7...
October 20, 2016: Physiological Research
Peter Bailey, David K Chang, Marie-Andrée Forget, Francis A San Lucas, Hector A Alvarez, Cara Haymaker, Chandrani Chattopadhyay, Sun-Hee Kim, Suhendan Ekmekcioglu, Elizabeth A Grimm, Andrew V Biankin, Patrick Hwu, Anirban Maitra, Jason Roszik
Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases...
October 20, 2016: Scientific Reports
Shinnosuke Ikemura, Nao Aramaki, Satoshi Fujii, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Takeshi Kuwata, Motohiro Kojima, Atsushi Ochiai, Tomoko Betsuyaku, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii
Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases...
October 20, 2016: Cancer Science
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