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tumor niche

Shuvasree SenGupta, Bhagawat C Subramanian, Carole A Parent
The directed migration of neutrophils to sites of injury or infection is mediated by complex networks of chemoattractant-receptor signaling cascades. The recent appreciation of neutrophils as active participants in tumor progression and metastasis has drawn attention to a number of chemokine-receptor systems that may drive their recruitment to tumors. However, the dynamic nature of the tumor microenvironment (TME) along with the phenotypic diversity among tumor-associated neutrophils (TANs) call for a more comprehensive approach to understand neutrophil trafficking to tumors...
December 14, 2018: Journal of Leukocyte Biology
Enrico Pierluigi Spugnini, Mariantonia Logozzi, Rossella Di Raimo, Davide Mizzoni, Stefano Fais
Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial⁻mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids...
December 10, 2018: International Journal of Molecular Sciences
Shangke Huang, Na Yuan, Guanying Wang, Fang Wu, Lu Feng, Minna Luo, Miao Li, Anqi Luo, Xinhan Zhao, Lingxiao Zhang
Networks of nanotubes and microtubules are highly valued in cellular communication, and collective cancer movement has been revealed to be associated with cell information exchange. In the present study, cellular communication was demonstrated to participate in mammosphere growth, differentiation and collective invasion. By promoting differentiation, networks of cells and microtubule‑like structures were verified. Analyses of cell cycle progression, stemness markers and gene expression indicated that mammospheres had collective characteristics of stemness and differentiation...
October 9, 2018: Oncology Reports
Mugurel Constantin Rusu, Florinel Pop, Sorin Hostiuc, Livia Manta, Nicoleta Măru, Mihai Grigoriu
Uterine leiomyomas, also known as uterine fibroids (UFs), are benign smooth muscle cells tumors, the most frequent tumors in women. Even though UFs are monoclonal tumors, they contain a heterogeneous and versatile cells population. There are scarce proofs about the processes of transdifferentiation that might occur in UFs, modify the tumor microenvironment and support blood and lymph vessels formation. The stromal niches of the UFs harbor cells with angiogenic∕lymphangiogenic, as well as with vasculogenic∕lymphvasculogenic potential, which belong to a phenotypic continuum between the endothelial and mesenchymal lineages...
2018: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Susmita Mondal, Kaushik Bhattacharya, Chitra Mandal
The emergence and maintenance of cancer stem-like cells (CSCs) are usually governed by tumor niche. Tumor niche always provides metabolic challenges to cancer cells and CSCs mostly because of tissue hypoxia. However, the role of micro-environmental nutritional stress (NS) in dedifferentiation of cancer cells is poorly defined. Here, we developed a stochastic model of CSCs by gradual nutritional deprivation in glioblastoma multiforme (GBM) cells used as a model system. Nutritional deprivation induced enhanced expression of glioblastoma stem-like cells (GSCs)-specific biomarkers with higher invasive and angiogenic properties...
2018: Cell Death Discovery
Sebastian A Wohlfeil, Verena Häfele, Bianca Dietsch, Kai Schledzewski, Manuel Winkler, Johanna Zierow, Thomas Leibing, Mona Malek Mohammadi, Joerg Heineke, Carsten Sticht, Victor Olsavszky, Philipp-Sebastian Koch, Cyrill Géraud, Sergij Goerdt
The interaction of tumor cells with organ-specific endothelial cells (EC) is an important step during metastatic progression. Notch signaling in organ-specific niches has been implicated in mediating opposing effects on organotropic metastasis to the lungs and the liver, respectively. In this study, we scrutinized the role of endothelial Notch activation during liver metastasis. To target hepatic EC (HEC), a novel EC subtype-specific Cre driver mouse was generated. Clec4g-Cretg/wt mice were crossed to Rosa26N1ICD IRES-GFP to enhance Notch signaling in HEC (NICDOE-HEC)...
December 10, 2018: Cancer Research
Michael Bartoschek, Nikolay Oskolkov, Matteo Bocci, John Lövrot, Christer Larsson, Mikael Sommarin, Chris D Madsen, David Lindgren, Gyula Pekar, Göran Karlsson, Markus Ringnér, Jonas Bergh, Åsa Björklund, Kristian Pietras
Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium...
December 4, 2018: Nature Communications
Junaid Raja, Johannes M Ludwig, Scott N Gettinger, Kurt A Schalper, Hyun S Kim
BACKGROUND: Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques...
December 4, 2018: Journal for Immunotherapy of Cancer
Malgorzata Czyz
Hepatocyte growth factor (HGF)/ mesenchymal-epithelial transition factor (c-MET) signaling is involved in complex cellular programs that are important for embryonic development and tissue regeneration, but its activity is also utilized by cancer cells during tumor progression. HGF and c-MET usually mediate heterotypic cell⁻cell interactions, such as epithelial⁻mesenchymal, including tumor⁻stroma interactions. In the skin, dermal fibroblasts are the main source of HGF. The presence of c-MET on keratinocytes is crucial for wound healing in the skin...
December 3, 2018: International Journal of Molecular Sciences
Valeriia Gulaia, Vadim Kumeiko, Nikita Shved, Eduardas Cicinskas, Stanislav Rybtsov, Alexey Ruzov, Alexander Kagansky
Cellular quiescence is a reversible, non-cycling state controlled by epigenetic, transcriptional and niche-associated molecular factors. Quiescence is a condition where molecular signaling pathways maintain the poised cell-cycle state whilst enabling rapid cell cycle re-entry. To achieve therapeutic breakthroughs in oncology it is crucial to decipher these molecular mechanisms employed by the cancerous milieu to control, maintain and gear stem cells towards re-activation. Cancer stem-like cells (CSCs) have been extensively studied in most malignancies, including glioma...
2018: Frontiers in Cellular Neuroscience
Paola Ortiz-Montero, Win-Yan Liu-Bordes, Arturo Londoño-Vallejo, Jean-Paul Vernot
Background: Most carcinomas are composed of heterogeneous populations of tumor cells with distinct and apparently stable phenotypic characteristics. Methods: Using an in vitro model of carcinogenesis we aimed at experimentally elucidating the significance of heterogeneity in the expression of CD24, a marker frequently overexpressed in various cancers and correlated with poor prognosis. Results: We show that CD24Neg and CD24Pos cells issued from the same tumorigenic cell line display striking differences in stem-related properties, expression of epithelial-mesenchymal transition/mesenchymal-epithelial transition markers, and tumorigenic capacity...
2018: Cancer Management and Research
Zhifei Dai, Sadaf Hameed, Hong Chen, Muhammad Irfan, Sadia Z Bajwa, Waheed Samraiz Khan, Shahid Mahmood Baig
For SLN lymph node biopsy (SLNB), the SLN mapping has become a standard of care procedure that can accurately locate the micrometastases disseminated from primary tumor sites to the regional lymph nodes. The broad array of SLN mapping has prompted the development of a wide range of SLN tracers, rationally designed for noninvasive, and high-resolution imaging of SLNs. At present, conventional SLN imaging probes (blue dyes, radiocolloids and few other small-molecular dyes) although serves the clinical needs, these are often associated with major issues such as insufficient accumulation in SLN, short retention time, staining of the surgical field and other adverse side effects...
December 3, 2018: Bioconjugate Chemistry
Yaroslav R Efremov, Anastasia S Proskurina, Ekaterina A Potter, Evgenia V Dolgova, Oksana V Efremova, Oleg S Taranov, Aleksandr A Ostanin, Elena R Chernykh, Nikolay A Kolchanov, Sergey S Bogachev
A functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. In the first part of the study, the genes were analyzed for their belonging to one or more of the three groups, which represent the three major phenotypic manifestation of malignancy of cancer cells, namely (1) proliferative self-sufficiency, (2) invasive growth and metastasis, and (3) multiple drug resistance. 96 genes out of 167 were identified as possible contributors to at least one of these fundamental properties...
2018: Frontiers in Genetics
Du Meng, Min Meng, Anqi Luo, Xin Jing, Guanying Wang, Shangke Huang, Minna Luo, Shan Shao, Xinhan Zhao, Rui Liu
The pre-metastatic niche has been shown to play a critical role in tumor metastasis, and its formation is closely related to the tumor microenvironment. However, the underlying molecular mechanisms remain unclear. In the present study, we successfully established a mouse model of lung metastasis using luciferase-expressing MDA-MB-435s cells. In this model, recruitment of vascular endothelial growth factor receptor-1 (VEGFR1)+ CD133+ hematopoietic progenitor cells (HPCs) was gradually increased in lung but gradually decreased after the formation of tumor colonies in lung...
November 27, 2018: Journal of Cancer Research and Clinical Oncology
Jing Jing Fu, Ying Zhou, Xiao Xiao Shi, Yue Jun Kang, Zhi Song Lu, Yuan Li, Chang Ming Li, Ling Yu
Emerging evidence has demonstrated that cancer stem cells (CSCs) play critical roles in tumor invasion, metastasis and recurrence. The specific targeting capability on CSCs is of high importance for the development of effective anti-tumor therapeutics. However, isolation, enrichment and cultivation of these special and rare groups of tumor cells for in vitro analyses is a nontrivial job and requires particular culture medium and environmental control. Herein, we established a low-cost and efficient method for CSC enrichment by culturing prostate cancer cells on a hydrophilic filter paper...
November 19, 2018: Colloids and Surfaces. B, Biointerfaces
Huan Cao, Melissa Kao Hui Lee, Haibo Yang, Siu Kwan Sze, Nguan Soon Tan, Chor Yong Tay
Tumor stromal residing cancer-associated fibroblasts (CAFs) are significant accomplices in the growth and development of malignant neoplasm. As cancer progresses, the stroma undergoes a dramatic remodeling and stiffening of its extracellular matrix (ECM). However, exactly how these biomechanical changes influence CAF behavior and the functional paracrine crosstalk with the neighboring tumor cells in a 3-dimensional (3D) microenvironment remains elusive. Herein, a collagen and alginate interpenetrating network (CoAl-IPN) hydrogel system was employed as a 3D in vitro surrogate of the cancerous breast tissue stromal niche...
November 27, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Eoin P McNeill, Robert W Reese, Abishek Tondon, Bret H Clough, Simin Pan, Jeremiah Froese, Daniel Palmer, Ulf Krause, David M Loeb, Roland Kaunas, Carl A Gregory
Malignant bone disease (MBD) occurs when tumors establish in bone, causing catastrophic tissue damage as a result of accelerated bone destruction and inhibition of repair. The resultant so-called osteolytic lesions (OL) take the form of tumor-filled cavities in bone that cause pain, fractures, and associated morbidity. Furthermore, the OL microenvironment can support survival of tumor cells and resistance to chemotherapy. Therefore, a deeper understanding of OL formation and MBD progression is imperative for the development of future therapeutic strategies...
November 26, 2018: Cell Death & Disease
Jaime Fornetti, Alana L Welm, Sheila A Stewart
The bone is the third most common site of metastasis for a wide range of solid tumors including lung, breast, prostate, colorectal, thyroid, gynecologic, and melanoma, with 70% of metastatic prostate and breast cancer patients harboring bone metastasis. Unfortunately, once cancer spreads to the bone, it is rarely cured and is associated with a wide range of morbidities including pain, increased risk of fracture, and hypercalcemia. This fact has driven experts in the fields of bone and cancer biology to study the bone, and has revealed that there is a great deal that each can teach the other...
November 26, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Raghupathy Vengoji, Moorthy P Ponnusamy, Satyanarayana Rachagani, Sidharth Mahapatra, Surinder K Batra, Nicole Shonka, Muzafar A Macha
Glioblastoma (GBM) is among the most aggressive brain tumors with a dismal prognosis. Despite significant advances in the current multimodality therapy including surgery, postoperative radiotherapy (RT) and temozolomide (TMZ) based concomitant and adjuvant chemotherapy (CT), tumor recurrence is nearly universal with poor patient outcome. These limitations are in part due to poor drug penetration through the blood brain barrier (BBB) and resistance to CT and RT by a small population of cancer cells recognized as tumor-initiating cells or cancer stem cells (CSCs)...
November 24, 2018: Carcinogenesis
Teresa Bernadette Steinbichler, József Dudás, Sergej Skvortsov, Ute Ganswindt, Herbert Riechelmann, Ira-Ida Skvortsova
Cancer stem cells (CSC) possess abilities generally associated with embryonic or adult stem cells, especially self-renewal and differentiation. The CSC model assumes that this subpopulation of cells sustains malignant growth, which suggests a hierarchical organization of tumors in which CSCs are on top and responsible for the generation of intratumoral heterogeneity. Effective tumor therapy requires the eradication of CSC as they can support regrowth of the tumor resulting in recurrence. However, eradication of CSC is difficult because they frequently are therapy resistant...
December 2018: Seminars in Cancer Biology
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