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Stroma mesenchymal

Catharina Melzer, Juliane von der Ohe, Ralf Hass
The tumor microenvironment enables important cellular interactions between cancer cells and recruited adjacent populations including mesenchymal stroma/stem cells (MSC). In vivo cellular interactions of primary human MSC in co-culture with human SK-OV-3 ovarian cancer cells revealed an increased tumor growth as compared to mono-cultures of the ovarian cancer cells. Moreover, the presence of MSC stimulated formation of liver metastases. Further interactions of MSC with the ovarian cancer cells resulted in the formation of hybrid cells by cell fusion...
October 13, 2018: Cell Communication and Signaling: CCS
Shao-Jie Chen, Guo-da Lian, Jia-Jia Li, Qiu-Bo Zhang, Lin-Juan Zeng, Ke-Ge Yang, Chu-Mei Huang, Ya-Qing Li, Yin-Ting Chen, Kai-Hong Huang
Tumor-associated macrophages (TAMs) are abundant population of inflammatory cells which play an essential role in remodeling tumor microenvironment and tumor progression. Previously, we found the high density of TAMs was correlated with lymph node metastasis and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Therefore, this study was designed to investigate the mechanisms of interaction between TAMs and PDAC. THP-1 monocytes were the exposure to conditioned media (CM) produced by PDAC cells; then, monocyte recruitment and macrophage differentiation were assessed...
October 12, 2018: Cancer Medicine
Felix Bremmer, Alexander Fichtner, Ralph Triefenbach, Reinhard Inniger, Peter Mayer, Laura Lukat, Philipp Ströbel, Hans Ulrich Schildhaus
In addition to germ cell tumors and tumors of the sex cord stroma, the WHO classification of testis and paratesticular tumors also contains malignant soft tissue tumors. Among them, liposarcomas of the spermatic cord are the most common entities. Other mesenchymal tumors with smooth muscle, skeletal muscle, fibroblastic/myofibroblastic, or nerve sheath differentiation are rare. Ewing sarcoma is composed of uniform small round cells and typically characterized by translocations of the EWSR1 gene. In rare cases, Ewing sarcoma-like tumors lack an EWSR1 gene fusion...
October 11, 2018: Virchows Archiv: An International Journal of Pathology
Patrizia Procacci, Claudia Moscheni, Patrizia Sartori, Michele Sommariva, Nicoletta Gagliano
The extracellular matrix (ECM) in the tumor microenvironment modulates the cancer cell phenotype, especially in pancreatic ductal adenocarcinoma (PDAC), a tumor characterized by an intense desmoplastic reaction. Because the epithelial-to-mesenchymal transition (EMT), a process that provides cancer cells with a metastatic phenotype, plays an important role in PDAC progression, the authors aimed to explore in vitro the interactions between human PDAC cells and ECM components of the PDAC microenvironment, focusing on the expression of EMT markers and matrix metalloproteinases (MMPs) that are able to digest the basement membrane during tumor invasion...
October 5, 2018: Cells
Marcin Kowanetz, Wei Zou, Scott N Gettinger, Hartmut Koeppen, Mark Kockx, Peter Schmid, Edward E Kadel, Ignacio Wistuba, Jamie Chaft, Naiyer A Rizvi, David R Spigel, Alexander Spira, Fred R Hirsch, Victor Cohen, Dustin Smith, Zach Boyd, Natasha Miley, Susan Flynn, Vincent Leveque, David S Shames, Marcus Ballinger, Simonetta Mocci, Geetha Shankar, Roel Funke, Garret Hampton, Alan Sandler, Lukas Amler, Ira Mellman, Daniel S Chen, Priti S Hegde
Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with non-small cell lung cancer (NSCLC) most likely to respond to single-agent checkpoint inhibitors. However, at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC: expression on TC or on tumor-infiltrating immune cells (ICs). We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4,549 cases of NSCLC...
October 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kazuhiko Morikawa, Shinsuke Takenaga, Koichi Masuda, Asami Kano, Takao Igarashi, Hiroya Ojiri, Kaoru Ueda, Mamoru Ishiyama, Nei Fukasawa
BACKGROUND: A solitary fibrous tumor (SFT) is a rare mesenchymal tumor that occurs mostly in pleural sites, and an SFT occurring in the ischiorectal fossa is extremely rare. Because of the rarity, there are few reports detailing an SFT in the ischiorectal fossa. CASE PRESENTATION: A pararectal tumor was incidentally found in a 42-year-old man during a routine medical examination. The patient had no symptoms and no previous medical history. In the physical examination, a smooth-margined and hard elastic mass was felt, and in a digital rectal examination, the rectal mucosa appeared normal...
October 3, 2018: Surgical Case Reports
Sonia Emilia Selicean, Ciprian Tomuleasa, Ravnit Grewal, Graca Almeida-Porada, Ioana Berindan-Neagoe
Primary myelofibrosis (PMF) is the most aggressive Philadelphia-negative (Ph-) myeloproliferative neoplasm (MPN), characterized by bone marrow (BM) insufficiency, myelofibrosis (MF), osteosclerosis, neoangiogenesis, and extramedullary hematopoiesis (EMH) in spleen and liver. Presently, there is no curative treatment for this disease and therapy consists primarily of symptom relief and, in selected cases, allogeneic hematopoietic stem cell transplant (alloHSCT). PMF's major defining characteristics, as well as several recently described aspects of its cellular and molecular pathophysiology all support a critical role for dysregulated cell-cell/cell-extracellular matrix interactions and cytokine/chemokine signaling within the BM niche in the natural history of this disease...
October 2, 2018: Leukemia & Lymphoma
Hotaka Kawai, Hidetsugu Tsujigiwa, Chong Huat Siar, Keisuke Nakano, Kiyofumi Takabatake, Masae Fujii, Mei Hamada, Ryo Tamamura, Hitoshi Nagatsuka
Background: The tumor microenvironment and its stromal cells play an important role in cancer development and metastasis. Bone marrow-derived cells (BMDCs), a rich source of hematopoietic and mesenchymal stem cells, putatively contribute to this tumoral stroma. However their characteristics and roles within the tumor microenvironment are unclear. In the present study, BMDCs in the tumor microenvironment were traced using the green fluorescent protein (GFP) bone marrow transplantation model. Methods: C57BL/6 mice were irradiated and rescued by bone marrow transplantation from GFP-transgenic mice...
2018: International Journal of Medical Sciences
Yongtian Yu, Liang Cheng, Bin Yan, Cancan Zhou, Weikun Qian, Ying Xiao, Tao Qin, Junyu Cao, Liang Han, Qingyong Ma, Jiguang Ma
Sonic hedgehog (SHH) signaling is an important promotor of desmoplasia, a critical feature in pancreatic cancer stromal reactions involving the activation of pancreatic stellate cells (PSCs). Gremlin 1 is widely overexpressed in cancer-associated stromal cells, including activated PSCs. In embryonic development, SHH is a potent regulator of Gremlin 1 through an interaction network. This subtle mechanism in the cancer microenvironment remains to be fully elucidated. The present study investigated the association between Gremlin 1 and SHH, and the effect of Gremlin 1 in pancreatic cancer...
September 26, 2018: International Journal of Oncology
Federica Portale, Giulia Cricrì, Silvia Bresolin, Monica Lupi, Stefania Gaspari, Daniela Silvestri, Barbara Russo, Noemi Marino, Paolo Ubezio, Fabio Pagni, Patrizia Vergani, Geertruy Te Kronnie, Maria Grazia Valsecchi, Franco Locatelli, Carmelo Rizzari, Andrea Biondi, Erica Dander, Giovanna D'Amico
B-cell precursor-Acute Lymphoblastic Leukemia modulates the bone marrow niche to become leukemia-supporting and chemoprotective by reprogramming the stromal microenvironment. New therapies targeting the leukemia/stroma interplay can be instrumental to improve disease outcome. We identified ActivinA, a TGF-β family member, with a well-described promoting role in several solid malignancies, as a new potentially targetable leukemia-favoring factor. ActivinA resulted overexpressed in the leukemic bone marrow and its production was strongly induced in mesenchymal stromal cells after culture with leukemic cells...
September 27, 2018: Haematologica
Kamil Kowalski, Matthieu Dos Santos, Pascal Maire, Maria A Ciemerych, Edyta Brzoska
BACKGROUND: Skeletal muscle regeneration is possible thanks to unipotent stem cells, which are satellite cells connected to the myofibers. Populations of stem cells other than muscle-specific satellite cells are considered as sources of cells able to support skeletal muscle reconstruction. Among these are bone marrow-derived mesenchymal stem cells (BM-MSCs), which are multipotent, self-renewing stem cells present in the bone marrow stroma. Available data documenting the ability of BM-MSCs to undergo myogenic differentiation are not definitive...
September 27, 2018: Stem Cell Research & Therapy
Daniel Clayton Morse, Jaime Tschen
We report a case of a slowly growing papule on the nasal bridge of an elderly woman. Histopathological findings revealed a very unusual type of folliculosebaceous cystic hamartoma with a retiform and primitive epithelial proliferation associated with the stromal component. Folliculosebaceous cystic hamartoma is an uncommon lesion that involves a cystically dilated follicle embedded in a stroma of distinct mesenchymal tissue. Because folliculosebaceous cystic hamartoma is a rare and clinically indistinct lesion, clinical photographs of the lesion are not widely available...
July 15, 2018: Dermatology Online Journal
Rui Caetano Oliveira, Fernando C Schmitt
BACKGROUND: The presence of highly cellular stromal fragments in breast fine needle aspirates (FNA) suggests some classical differential diagnoses such as cellular fibroadenoma, phyllodes tumour (PT), metaplastic carcinomas, and some mesenchymal/myoepithelial proliferations. The other components of the smears can help in the differential diagnosis, but the presence of a low-grade epithelial proliferation does not always represent a fibro-epithelial lesion as we demonstrate in these two cases...
September 24, 2018: Acta Cytologica
Gracjana Krzysiek-Maczka, Aneta Targosz, Urszula Szczyrk, Malgorzata Strzałka, Zbigniew Sliwowski, Tomasz Brzozowski, Jarosław Czyz, Agata Ptak-Belowska
BACKGROUND: Major human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori-infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H...
September 23, 2018: Helicobacter
Maurizio Mangolini, Frederik Götte, Andrew Moore, Tim Ammon, Madlen Oelsner, Gloria Lutzny-Geier, Ludger Klein-Hitpass, James C Williamson, Paul J Lehner, Jan Dürig, Michael Möllmann, Lívia Rásó-Barnett, Katherine Hughes, Antonella Santoro, Simón Méndez-Ferrer, Robert A J Oostendorp, Ursula Zimber-Strobl, Christian Peschel, Daniel J Hodson, Marc Schmidt-Supprian, Ingo Ringshausen
The Wnt signalling pathway, one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL), is activated in only a subset of patients through somatic mutations. Here we describe alternative, microenvironment-dependent mechanisms of Wnt activation in malignant B cells. We show that tumour cells specifically induce Notch2 activity in mesenchymal stromal cells (MSCs) required for the transcription of the complement factor C1q. MSC-derived C1q in turn inhibits Gsk3-β mediated degradation of β-catenin in CLL cells...
September 21, 2018: Nature Communications
Kotryna Seip, Kjetil Jørgensen, Marco Vincent Haselager, Marco Albrecht, Mads Haugland Haugen, Eivind Valen Egeland, Philippe Lucarelli, Olav Engebraaten, Thomas Sauter, Gunhild Mari Mælandsmo, Lina Prasmickaite
Cancer cells' phenotypic plasticity, promoted by stromal cells, contributes to intra-tumoral heterogeneity and affects response to therapy. We have disclosed an association between fibroblast-stimulated phenotype switching and resistance to the clinically used BRAF inhibitor (BRAFi) vemurafenib in malignant melanoma, revealing a challenge in targeting the fibroblast-induced phenotype. Here we compared molecular features and drug sensitivity in melanoma cells grown as co-cultures with fibroblasts versus mono-cultures...
September 18, 2018: Cancer Letters
Christina Schug, Aayush Gupta, Sarah Urnauer, Katja Steiger, Phyllis Fung-Yi Cheung, Christian Neander, Konstantinos Savvatakis, Kathrin A Schmohl, Marija Trajkovic-Arsic, Nathalie Schwenk, Markus Schwaiger, Peter J Nelson, Jens T Siveke, Christine Spitzweg
The sodium iodide symporter ( SLC5A5/NIS ) as theranostic gene would allow for non-invasive imaging of functional NIS expression and therapeutic radioiodine application. Genetically engineered mesenchymal stem cells (MSC), based on their tumor-homing abilities, show great promise as tumor-selective NIS gene delivery vehicles for non-thyroidal tumors. As a next step towards clinical application, tumor specificity and efficacy of MSCs were investigated in an advanced genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC)...
September 17, 2018: Molecular Cancer Research: MCR
Jin Wang, Tianfang Wang, Yanfang Sun, Yuan Feng, William C Kisseberth, Carolyn J Henry, Irene Mok, Susan E Lana, Kevin Dobbin, Nicole Northrup, Elizabeth W Howerth, Shaying Zhao
Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor overactivated WNT/β-catenin pathways and recurrent CTNNB1 (β-catenin) mutations S45F/P, D32Y and G34E. Invasive canine tumors harbor prominent fibroblast proliferation and overactivated stroma...
September 14, 2018: Cancers
Yang Liu, Wanting Cao, Xiangbo Kong, Jie Li, Xueying Chen, Yaping Ge, Wanzhen Zhong, Silian Fang
Osteoradionecrosis of the jaws (ORNJ) is a complication of oral and maxillofacial malignancy that arises following radiotherapy; progressive jaw necrosis severely decreases the quality of life of patients. Human bone marrow mesenchymal stem cells (hBMMSCs) are a cell type with self‑renewal and pluripotent differentiation potential in the bone marrow stroma. These cells are associated with bone tissue regeneration and are one of the primary cell types affected by bone tissue radiation injury. α‑2‑macroglobulin (α2M) is a glycoprotein‑rich macromolecule that interacts with cytokines, growth factors and hormones to serve a variety of biological roles...
September 4, 2018: Molecular Medicine Reports
Q X Gong, Z H Zhang, Q H Fan
Objective: To study clinicopathologic features, diagnosis and differential diagnosis of myxoid variant of angiomatoid fibrous histiocytoma (AFH). Methods: Three cases of myxoid variant of AFHs were collected from First Affiliated Hospital of Nanjing Medical University during 2008 and 2017. EnVision method and fluorescence in situ hybridization(FISH) were used to detect immunophenotype and EWSR1 gene rearrangement, respectively. Results: There were 2 males and l female with age at 13, 31, and 42 years, respectively...
September 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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