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mesenchymal stem cells cancer

Wojciech Marlicz, Katarzyna Sielatycka, Karol Serwin, Ewa Kubis, Marta Tkacz, Rafał Głuszko, Andrzej Białek, Teresa Starzyńska, Mariusz Z Ratajczak
Bone marrow (BM) residing stem cells are mobilized from their BM niches into peripheral blood (PB) in several pathological situations including tissue organ injury and systemic inflammation. We recently reported that the number of BM-derived stem cells (SCs) increases in patients with pancreatic and stomach cancer. Accordingly, we observed higher numbers of circulating very small embryonic/epiblast‑like stem cells (VSELs) and mesenchymal stem cells (MSCs) that were associated with the activation of pro-mobilizing complement cascade and an elevated level of sphingosine-1 phosphate (S1P) in PB plasma...
October 18, 2016: Oncology Reports
Xuan Zhou, Wei Zhu, Margaret Nowicki, Shida Miao, Haitao Cui, Benjamin Holmes, Robert I Glazer, Lijie Grace Zhang
Metastasis is one of the deadliest consequences of breast cancer, with bone being one of the primary sites of occurrence. Insufficient 3D biomimetic models currently exist to replicate this process in vitro. In this study, we developed a biomimetic bone matrix using 3D bioprinting technology to investigate the interaction between breast cancer (BrCa) cells and bone stromal cells (fetal osteoblasts and human bone marrow mesenchymal stem cells (MSCs)). A tabletop stereolithography 3D bioprinter was employed to fabricate a series of bone matrices consisting of osteoblasts/MSCs encapsulated in gelatin methacrylate (GelMA) hydrogel with nanocrystalline hydroxyapatite (nHA)...
October 21, 2016: ACS Applied Materials & Interfaces
Sara Zahedi, Karim Shamsasenjan, Aliakbar Movassaghpour, Parvin Akbarzadehlaleh
Purpose: Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy...
September 2016: Advanced Pharmaceutical Bulletin
Peixin Dong, Ying Xiong, Hidemichi Watari, Sharon Jb Hanley, Yosuke Konno, Kei Ihira, Fumihiko Suzuki, Takahiro Yamada, Masataka Kudo, Junming Yue, Noriaki Sakuragi
Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels...
October 21, 2016: Scientific Reports
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
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
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Jamal El-Saghir, Farah Nassar, Nadim Tawil, Marwan El-Sabban
BACKGROUND: Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia...
October 19, 2016: Retrovirology
Xin-Yu Zhao, Lei Li, Xiao-Bo Wang, Rong-Jie Fu, Ya-Ping Lv, Wei Jin, Chao Meng, Guo-Qiang Chen, Lei Huang, Ke-Wen Zhao
China accounts for almost half of the total number of liver cancer cases and deaths worldwide, and hepatocellular carcinoma (HCC) is the most primary liver cancer. Snail family transcriptional repressor 2 (SNAI2) is known as an epithelial to mesenchymal transition-inducing transcription factor that drives neoplastic epithelial cells into mesenchymal phenotype. However, the roles of endogenous SNAI2 remain controversial in different types of malignant tumors. Herein, we surprisingly identify that anchorage-independent growth, including the formation of tumor sphere and soft agar colony, is significantly increased when SNAI2 expression is inhibited by shRNAs in HCC cells...
2016: PloS One
Andrea Moretti, Jianfeng Li, Stefano Donini, Robert W Sobol, Menico Rizzi, Silvia Garavaglia
The aldehyde dehydrogenase family 1 member A3 (ALDH1A3) catalyzes the oxidation of retinal to the pleiotropic factor retinoic acid using NAD(+). The level of ALDHs enzymatic activity has been used as a cancer stem cell marker and seems to correlate with tumour aggressiveness. Elevated ALDH1A3 expression in mesenchymal glioma stem cells highlights the potential of this isozyme as a prognosis marker and drug target. Here we report the first crystal structure of human ALDH1A3 complexed with NAD(+) and the product all-trans retinoic acid (REA)...
October 19, 2016: Scientific Reports
Meiou Dai, Chenjing Zhang, Ayad Ali, Xinyuan Hong, Jun Tian, Chieh Lo, Nadège Fils-Aimé, Sergio A Burgos, Suhad Ali, Jean-Jacques Lebrun
Triple negative breast cancers exhibit very aggressive features and poor patient outcomes. These tumors are enriched in cancer stem cells and exhibit resistance to most treatments and chemotherapy. In this study, we found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. We found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients...
October 19, 2016: Scientific Reports
Adam R Wolfe, Nicholaus J Trenton, Bisrat G Debeb, Richard Larson, Brian Ruffell, Khoi Chu, Walter Hittelman, Michael Diehl, Jim M Reuben, Naoto T Ueno, Wendy A Woodward
Inflammatory breast cancer (IBC) is a unique and deadly disease with unknown drivers. We hypothesized the inflammatory environment contributes to the IBC phenotype. We used an in vitro co-culture system to investigate interactions between normal and polarized macrophages (RAW 264.7 cell line), bone-marrow derived mesenchymal stem cells (MSCs), and IBC cells (SUM 149 and MDA-IBC3). We used an in vivo model that reproduces the IBC phenotype by co-injecting IBC cells with MSCs into the mammary fat pad. Mice were then treated with a macrophage recruitment inhibitor, anti-CSF1...
October 15, 2016: Oncotarget
Tao Yin, Guoping Wang, Sisi He, Guobo Shen, Chao Su, Yan Zhang, Xiawei Wei, Tinghong Ye, Ling Li, Shengyong Yang, Dan Li, Fuchun Guo, Zemin Mo, Yang Wan, Ping Ai, Xiaojuan Zhou, Yantong Liu, Yongsheng Wang, Yuquan Wei
Malignant pleural effusion (PE) and ascites, common clinical manifestations in advanced cancer patients, are associated with poor prognosis. However, the biological characteristics of malignant PE and ascites are not clarified. Here, we report that malignant PE and ascites can induce frequent epithelial-mesenchymal transition (EMT) program and endow tumor cells with stem cell properties with high efficiency, which promote tumor growth, chemoresistance and immune evasion. We determine that this EMT process is mainly dependent on VEGF, one initiator of PI3K/Akt/mTOR pathway...
October 18, 2016: Journal of Biological Chemistry
Monica D Prakash, Sarah Miller, Sarron Randall-Demllo, Kulmira Nurgali
Cancer development is often associated with chronic inflammation. To date, research into inflammation-induced cancer has largely focused on chemokines, cytokines, and their downstream targets. These inflammatory mediators may promote tumor growth, invasion, metastasis, and facilitate angiogenesis. However, the exact mechanisms by which inflammation promotes neoplasia remain unclear. Inflammatory bowel disease (IBD) is characterized by recurrent, idiopathic intestinal inflammation, the complications of which are potentially fatal...
November 2016: Inflammatory Bowel Diseases
Le Zhang, Liang Xu, Fengchun Zhang, Erina Vlashi
Experimental evidence suggest that breast tumors originate from breast cancer stem cells (BCSCs), and that mitochondrial biogenesis is essential for the anchorage-independent clonal expansion and survival of CSCs, thus rendering mitochondria a significant target for novel treatment approaches. One of the recognized side effects of the FDA-approved drug, doxycycline is the inhibition of mitochondrial biogenesis. Here we investigate the mechanism by which doxycycline exerts its inhibitory effects on the properties of breast cancer cells and BCSCs, such as mammosphere forming efficiency, invasion, migration, apoptosis, the expression of stem cell markers and epithelial-to-mesenchymal transition (EMT) related markers of breast cancer cells...
October 18, 2016: Cell Cycle
Qing Yang, Yingqiu Xie, Lixia Miao
Cancers induced by gene mutation, deletion, and genome instability might be related to aging. With similar pathways of aging but distinct functions, senescence at the cellular level is an irreversible arrest of cell cycle. Senescence has long been believed as a barrier to restrict tumor expansion. However, more and more evidence has been shown that senescence inducers regulate epithelial-mesenchymal transition, stem cell self-renewal, inflammatory response, crosstalk with the oncogenic bypass signaling, and conversion of oncogene to tumor suppressor...
October 18, 2016: Cancer Investigation
Deeksha Pal, Venkatesh Kolluru, Balaji Chanderashekar, Becca V Baby, Mazzy Aman, Suman Suman, Suman Sirimulla, Mary Ann Sanders, Praveen Seshabhatter, Houda Alatassi, Murali K Ankem, Chendil Damodaran
We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues...
October 18, 2016: Molecular Carcinogenesis
Vasilina A Sergeeva, Svetlana V Kostyuk, Elizaveta S Ershova, Elena M Malinovskaya, Tatiana D Smirnova, Larisa V Kameneva, Natalia N Veiko
It has been established that cell-free DNA circulating in the bloodstream affects cells. The characteristics of cfDNA depend on the physiological state of the organism. As we showed previously, diseases can cause either GC-enrichment of the cell-free DNA pool or its oxidation. Thus, in cases of cerebral atherosclerosis, heart attack and rheumatic arthritis the cell-free DNA pool is GC-enriched and, in the case of cancer, both GC-enriched and oxidized. Herein we investigated the time-dependent effect of oxidized and GC-rich cell-free DNA on NF-kB and NRF2 signaling pathways in human mesenchymal stem cells and showed that they affect cells in different ways...
2016: Advances in Experimental Medicine and Biology
Yaser Atlasi, Rubina Noori, Ivana Marolin, Patrick Franken, Joana Brandao, Katharina Biermann, Paola Collini, Mariam Grigorian, Eugene Lukanidin, Noona Ambartsumian, Riccardo Fodde
INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis. METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models. RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract...
October 14, 2016: European Journal of Cancer
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