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Stroma mesenchymal

Gen Nishikawa, Kenji Kawada, Jun Nakagawa, Kosuke Toda, Ryotaro Ogawa, Susumu Inamoto, Rei Mizuno, Yoshiro Itatani, Yoshiharu Sakai
Mesenchymal stem cells (MSCs) are recruited from BM to the stroma of developing tumors, where they serve as critical components of the tumor microenvironment by secreting growth factors, cytokines, and chemokines. The role of MSCs in colorectal cancer (CRC) progression was controversial. In this study, we found that C-C chemokine receptor type 5 (CCR5) ligands (i.e., C-C motif chemokine ligand 3 (CCL3), CCL4, and CCL5) were highly produced from MSCs using a chemokine array screening with conditioned media from the cultured human MSCs...
March 19, 2019: Cell Death & Disease
Jiamin Chen, Billy T Lau, Noemi Andor, Susan M Grimes, Christine Handy, Christina Wood-Bouwens, Hanlee P Ji
The diverse cellular milieu of the gastric tissue microenvironment plays a critical role in normal tissue homeostasis and tumor development. However, few cell culture model can recapitulate the tissue microenvironment and intercellular signaling in vitro. We used a primary tissue culture system to generate a murine p53 null gastric tissue model containing both epithelium and mesenchymal stroma. To characterize the microenvironment and niche signaling, we used single cell RNA sequencing (scRNA-Seq) to determine the transcriptomes of 4,391 individual cells...
March 14, 2019: Scientific Reports
Chelsea Chandler, Tianshi Liu, Ronald Buckanovich, Lan G Coffman
Cancer-associated fibrosis is a critical component of the tumor microenvironment (TME) which significantly impacts cancer behavior. However, there is significant controversy regarding fibrosis as a predominantly tumor promoting or tumor suppressing factor. Cells essential to the generation of tissue fibrosis such as fibroblasts and mesenchymal stem cells (MSCs) have dual phenotypes dependent upon their independence or association with cancer cells. Cancer-associated fibroblasts and cancer-associated MSCs have unique molecular profiles which facilitate cancer cell cross talk, influence extracellular matrix deposition, and direct the immune system to generate a protumorigenic environment...
February 21, 2019: Translational Research: the Journal of Laboratory and Clinical Medicine
Douglas Saforo, Linda Omer, Andrei Smolenkov, Aditya Barve, Lavona Casson, Nolan Boyd, Geoffrey Clark, Leah Siskind, Levi Beverly
The tumor microenvironment (TME) is composed of a heterogeneous biological ecosystem of cellular and non-cellular elements including transformed tumor cells, endothelial cells, immune cells, activated fibroblasts or myofibroblasts, stem and progenitor cells, as well as the cytokines and matrix that they produce. The constituents of the TME stroma are multiple and varied, however cancer associated fibroblasts (CAF) and their contribution to the TME are important in tumor progression. CAF are hypothesized to arise from multiple progenitor cell types, including mesenchymal stem cells...
March 12, 2019: Scientific Reports
Masahiro Yoshida, Hiroto Horiguchi, Shohei Kikuchi, Satoshi Iyama, Hiroshi Ikeda, Akari Goto, Yutaka Kawano, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Junji Kato, Masayoshi Kobune
We and others have demonstrated that various abnormalities of the bone marrow (BM) mesenchymal stromal cells (MSCs) such as aberrant cytokine expression, abnormal hedgehog signaling, and impaired miRNA biogenesis are observed in patients with acute myeloid leukemia (AML). However, underlying mechanisms to induce the dysfunction of BM MSCs have not yet been clarified. We previously showed that AML cells release abundant exosomal miR-7977, which, in turn, enters BM mesenchymal stromal cells (MSCs). However, the precise function of miR-7977 is not known...
2019: PloS One
Zhangye Xu, Shenzhi Zhao, Tong Zhou, Tingting Liao, Xianping Huang, Huiqiu Xiang, Qiong Zhang, Yanjun Huang, Feng Lin, Duyun Ye, Yinping Huang
PROBLEM: To assess whether lipoxin A4 (LXA4) interferes with embryo implantation via epithelial-mesenchymal transition (EMT) suppression. METHOD OF STUDY: We developed a mouse model of LXA4 blocked embryo implantation, and detected EMT indicators to confirm that LXA4 associated EMT suppression might be a mechanism of interfering with embryo implantation. ILK, FPR2, VEGF, MMPs, Akt, GSK3β, NF-ĸB, Twist, vimentin, fibronectin and β-catenin mRNA levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR; while protein localization and amounts were assessed by immunohistochemistry and Western blot, respectively; MMP activity was assessed by the gelatin zymography, The status of implantation in pregnant animals was assessed by the Pontamine blue reaction test...
February 27, 2019: American Journal of Reproductive Immunology: AJRI
Diego Segala, Stefano Gobbo, Anna Pesci, Guido Martignoni, Angela Santoro, Giuseppe Angelico, Damiano Arciuolo, Saveria Spadola, Michele Valente, Giovanni Scambia, Gian Franco Zannoni
It is well known that a large number of patients treated with Tamoxifen develops endometrial pathologies ranging from benign endometrial polyps and hyperplasia to adenocarcinomas, carcinosarcomas and adenosarcomas. UTROSCT (Uterine Tumor Resembling Ovarian Sex Cord Tumor) is defined as a mesenchymal tumors of the uterine corpus that morphologically resembles ovarian sex cord tumors, without recognizable endometrial stroma. To date only 4 cases have been reported in patients treated with tamoxifen. In this article, we describe an additional case occurring in a 62-years-old patient undergoing 3 years of Tamoxifen therapy for bilateral breast carcinoma...
January 28, 2019: Pathology, Research and Practice
Sanja Aveic, Roswitha Davtalab, Michael Vogt, Michael Weber, Patricia Buttler, Gian Paolo Tonini, Horst Fischer
Metastasis of tumor cells in the bone marrow (BM) is a multi-step and highly dynamic process during which cells succumb important phenotypic changes. Behavior of disseminated tumor cells in BM is strictly regulated by three-dimensional (3D) cell-cell and cell-matrix interactions. In this study, we explored whether the β-tricalcium-phosphate (β-TCP) scaffolds with a tailored interconnecting channel structure could enable appropriate 3D mimetic BM microenvironment for the growth of metastatic neuroblastoma cells...
February 20, 2019: Acta Biomaterialia
Sara N Meyer, José A Galván, Stefan Zahnd, Lena Sokol, Heather Dawson, Alessandro Lugli, Inti Zlobec
Tumor buds in colorectal cancer are hypothesized to undergo a (partial) epithelial-mesenchymal transition (EMT). If so, Cytokeratin (CK) and Vimentin (VIM) co-expression is expected. CK+/VIM+ can also be found in some stromal cells, however their origin remains unclear. Here, we determine the frequency of CK+/VIM+ tumor cells and characterize the CK+/VIM+ stroma in colorectal cancer. Three cell populations (CK+, VIM+ CK+/VIM+) were sorted using DepArray and Fluorescence Activated Cell Sorting (FACS). Tumor areas were selected to include tumor center, stroma and tumor budding...
February 19, 2019: Human Pathology
Xuefeng Kang, Yong Sun, Zhao Zhang
Human mesenchymal stem cells (hMSCs) have the capacity to differentiate into fabricate cartilage, muscle, marrow stroma, tendon/ligament, fat, and other connective tissues, providing a potential source for tissue regeneration. The aim of this study was to find the key transcription factors (TFs), which regulated osteogenic differentiation of hMSCs. In this study, three methods were performed to find the key TFs, which included enrichment analysis, direct impact value and indirect impact value. We used the patient and public involvements (PPI) network to integrate the results of the above methods for analysis...
March 2019: Experimental and Therapeutic Medicine
Ningning Li, Roya Babaei-Jadidi, Federica Lorenzi, Bradley Spencer-Dene, Philip Clarke, Enric Domingo, Eugene Tulchinsky, Robert G J Vries, David Kerr, Yihang Pan, Yulong He, David O Bates, Ian Tomlinson, Hans Clevers, Abdolrahman S Nateri
Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial-mesenchymal transition (EMT) process. Currently, it remains poorly understood how EMT programmes enable CSCs residing in the tumour microenvironment to escape the effects of chemotherapy. This study identifies a key molecular pathway that is responsible for the formation of drug-resistant CSC populations...
February 19, 2019: Oncogenesis
Catharina Melzer, Juliane von der Ohe, Ralf Hass
Cell fusion as a rare event was observed following the co-culture of human MDA-MB-231cherry breast cancer cells or benign neoplastic MCF10Acherry breast epithelial cells together with different mesenchymal stroma/stem-like cells (MSCGFP ) cultures, respectively, resulting in the generation of double-fluorescing hybrid cells. Analysis of potential molecular mechanisms for the formation of cancer hybrid cells revealed cytoskeletal components, including F-actin. Thus, a sub-lethal concentration of cytochalasin D, which blocks elongation of actin filaments, was able to significantly reduce cancer hybrid cell formation...
February 18, 2019: International Journal of Molecular Sciences
Hiroki Kobayashi, Atsushi Enomoto, Susan L Woods, Alastair D Burt, Masahide Takahashi, Daniel L Worthley
The tumour microenvironment, also termed the tumour stroma or tumour mesenchyme, includes fibroblasts, immune cells, blood vessels and the extracellular matrix and substantially influences the initiation, growth and dissemination of gastrointestinal cancer. Cancer-associated fibroblasts (CAFs) are one of the critical components of the tumour mesenchyme and not only provide physical support for epithelial cells but also are key functional regulators in cancer, promoting and retarding tumorigenesis in a context-dependent manner...
February 18, 2019: Nature Reviews. Gastroenterology & Hepatology
Catharina Melzer, Juliane von der Ohe, Ralf Hass
Cellular communication within the tumor microenvironment enables important interactions between cancer cells and recruited adjacent populations including mesenchymal stroma/stem-like cells (MSC). These interactions were monitored in vivo following co-injection of GFP-labeled human MSC together with mcherry-labeled MDA-MB-231 breast cancer cells in NODscid mice. Within 14 days of tumor development the number of initially co-injected MSC had significantly declined and spontaneous formation of breast cancer/MSC hybrid cells was observed by the appearance of double fluorescing cells...
February 5, 2019: Cancers
Carlotta Spano, Giulia Grisendi, Giulia Golinelli, Filippo Rossignoli, Malvina Prapa, Marco Bestagno, Olivia Candini, Tiziana Petrachi, Alessandra Recchia, Francesca Miselli, Giulia Rovesti, Giulia Orsi, Antonino Maiorana, Paola Manni, Elena Veronesi, Maria Serena Piccinno, Alba Murgia, Massimo Pinelli, Edwin M Horwitz, Stefano Cascinu, Pierfranco Conte, Massimo Dominici
Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive adult cancers with an unacceptable prognosis. For this reason novel therapies accounting for PDAC peculiarities, such as the relevant stromal reaction, are urgently needed. Here adipose mesenchymal stromal/stem cells (AD-MSC) have been armed to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related apoptosis-inducing ligand (sTRAIL). This cancer gene therapy strategy was in vitro challenged demonstrating that sTRAIL was thermally stable and able to induce apoptosis in the PDAC lines BxPC-3, MIA PaCa-2 and against primary PDAC cells...
February 11, 2019: Scientific Reports
Marco Franchi, Valentina Masola, Gloria Bellin, Maurizio Onisto, Konstantinos-Athanasios Karamanos, Zoi Piperigkou
: Interactions of cancer cells with matrix macromolecules of the surrounding tumor stroma are critical to mediate invasion and metastasis. In this study, we reproduced the collagen mechanical barriers in vitro (i.e., basement membrane, lamina propria under basement membrane, and deeper bundled collagen fibers with different array). These were used in 3D cell cultures to define their effects on morphology and behavior of breast cancer cells with different metastatic potential (MCF-7 and MDA-MB-231) using scanning electron microscope (SEM)...
February 7, 2019: Journal of Clinical Medicine
Basem M Abdallah, Abdullah M Alzahrani, Ashraf M Abdel-Moneim, Nicholas Ditzel, Moustapha Kassem
Background: Bone marrow derived stromal stem cells (BMSCs) are a clonogenic cell population that is characterized by self-renewal capacity and differentiation potential into osteoblasts, and other mesenchymal cell types. Mouse BMSCs (mBMSCs) are difficult to be cultured and propagated in vitro due to their replicative senescent phenotype, heterogeneity and high contamination with plastic adherent hematopoietic progenitors (HPCs). In this study, we described long-term culture of homogenous population of mBMSCs using simple and highly reproducible approach based on frequent subculturing (FS) at fixed split ratio in the presence of basic fibroblast growth factor (bFGF)...
2019: Biological Procedures Online
Tae-Min Kim, Yoon Ho Ko, Shin Jung Ha, Han Hong Lee
BACKGROUND: The CD133 transmembrane protein is a well-recognized stem cell marker that has been used to isolate putative cancer stem cell populations from gastric cancers (GCs). However, the molecular features or biomarkers underlying CD133 are largely unknown in GCs. METHODS: We performed gene expression profiling of CD133+ and CD133- cells sorted by flow cytometry from three GC cell lines to identify the CD133 expression signatures of GC. The CD133 expression signatures were investigated across publicly available expression profiles of multiple tumor types including GC and also for their relationship with patient survival...
February 4, 2019: BMC Cancer
Khin Thway, Cyril Fisher
Among the various genes that can be rearranged in soft tissue neoplasms associated with nonrandom chromosomal translocations, EWSR1 is the most frequent one to partner with other genes to generate recurrent fusion genes. This leads to a spectrum of clinically and pathologically diverse mesenchymal and nonmesenchymal neoplasms, variably manifesting as small round cell, spindle cell, clear cell or adipocytic tumors, or tumors with distinctive myxoid stroma. This review summarizes the growing list of mesenchymal neoplasms that are associated with EWSR1 gene rearrangements...
March 2019: Surgical Pathology Clinics
Ga-Young Lee, Seon-Yeong Jeong, Hae-Ri Lee, Il-Hoan Oh
The bone marrow (BM) microenvironment serves as a stem cell niche regulating the in vivo cell fate of normal hematopoietic stem cells (HSC) as well as leukemia stem cells (LSCs). Accumulating studies have indicated that the regeneration of normal HSCs and the process of leukemogenesis change with advancing age. However, the role of microenvironmental factors in these age-related effects are unclear. Here, we compared the stem cell niche in neonatal and adult BM to investigate potential differences in their microenvironmental regulation of both normal and leukemic stem cells...
January 30, 2019: Scientific Reports
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