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Tumor dormancy

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https://www.readbyqxmd.com/read/28202775/winter-is-coming-tumor-cells-go-into-hibernation
#1
Amanda W Lund
In response to hypoxia in the primary tumor microenvironment, tumor cells induce a state of dormancy enabling their persistence at metastatic sites and resistance to therapy.
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28197538/cancer-cell-cannibalism-and-the-sasp-ripples-in-the-murky-waters-of-tumor-dormancy
#2
Thomas J Bartosh
Relapse in cancer patients following an apparent cure and a prolonged latency period, known as tumor dormancy, remains an unrelenting clinical crisis. Here, I expand on our recent findings that potentially link cancer cell cannibalism of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to the senescence-associated secretory phenotype (SASP) and tumor dormancy.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28196146/chemotherapy-induces-adaptive-drug-resistance-and-metastatic-potentials-via-phenotypic-cxcr4-expressing-cell-state-transition-in-ovarian-cancer
#3
Hyun Hee Lee, Vanessa Bellat, Benedict Law
Ovarian cancer (OVC) patients who receive chemotherapy often acquire drug resistance within one year. This can lead to tumor reoccurrence and metastasis, the major causes of mortality. We report a transient increase of a small distinctive CXCR4High/CD24Low cancer stem cell population (CXCR4High) in A2780 and SKOV-3 OVC cell lines in response to cisplatin, doxorubicin, and paclitaxel, treatments. The withdrawal of the drug challenges reversed this cell-state transition. CXCR4High exhibits dormancy in drug resistance and mesenchymal-like invasion, migration, colonization, and tumor formation properties...
2017: PloS One
https://www.readbyqxmd.com/read/28115701/induction-of-dormancy-in-hypoxic-human-papillomavirus-positive-cancer-cells
#4
Karin Hoppe-Seyler, Felicitas Bossler, Claudia Lohrey, Julia Bulkescher, Frank Rösl, Lars Jansen, Arnulf Mayer, Peter Vaupel, Matthias Dürst, Felix Hoppe-Seyler
Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28039473/nanometronomic-treatment-of-4t1-breast-cancer-with-nanocaged-doxorubicin-prevents-drug-resistance-and-circumvents-cardiotoxicity
#5
Serena Mazzucchelli, Michela Bellini, Luisa Fiandra, Marta Truffi, Maria A Rizzuto, Luca Sorrentino, Erika Longhi, Manuela Nebuloni, Davide Prosperi, Fabio Corsi
Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach. However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, "metronomic" chemotherapy is based on frequent drug administrations at lower doses, resulting in neovascularization inhibition and induction of tumor dormancy. Here we show the potential of H-ferritin (HFn)-mediated targeted nanodelivery of metronomic doxorubicin (DOX) in the setting of a highly aggressive and metastatic 4T1 breast cancer mouse model with DOX-inducible expression of chemoresistance...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28039467/targeting-cancer-stem-cell-propagation-with-palbociclib-a-cdk4-6-inhibitor-telomerase-drives-tumor-cell-heterogeneity
#6
Gloria Bonuccelli, Maria Peiris-Pages, Bela Ozsvari, Ubaldo E Martinez-Outschoorn, Federica Sotgia, Michael P Lisanti
In this report, we systematically examined the role of telomerase activity in lung and ovarian cancer stem cell (CSC) propagation. For this purpose, we indirectly gauged telomerase activity, by linking the hTERT-promoter to eGFP. Using lung (A549) and ovarian (SKOV3) cancer cells, transduced with the hTERT-GFP reporter, we then employed GFP-expression levels to fractionate these cell lines into GFP-high and GFP-low populations. We functionally compared the phenotype of these GFP-high and GFP-low populations...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031411/a-systematic-analysis-of-negative-growth-control-implicates-the-dream-complex-in-cancer-cell-dormancy
#7
James MacDonald, Yudith Ramos-Valdes, Piru Perampalam, Larisa Litovchick, Gabriel E DiMattia, Frederick A Dick
: Epithelial ovarian cancer (EOC) generates multicellular aggregates called spheroids that detach from the primary tumor and disseminate through ascites. Spheroids possess a number of characteristics of tumor dormancy including withdrawal from the cell cycle and resistance to chemotherapeutics. This report systematically analyzes the effects of RNAi depletion of 21 genes that are known to contribute to negative regulation of the cell cycle in 10 ovarian cancer cell lines. Interestingly, spheroid cell viability was compromised by loss of some Cyclin Dependent Kinase Inhibitors such as p57Kip2, as well as Dyrk1A, Lin52, and E2F5 in most cell lines tested...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28017284/tumor-cell-dormancy
#8
REVIEW
Roger R Gomis, Sylwia Gawrzak
Metastasis is the primary cause of death in cancer patients and current treatments fail to provide durable responses. Efforts to treat metastatic disease are hindered by the fact that metastatic cells often remain dormant for prolonged intervals of years, or even decades. Tumor dormancy reflects the capability of disseminated tumor cells (DTCs), or micrometastases, to evade treatment and remain at low numbers after primary tumor resection. Unfortunately, dormant cells will eventually produce overt metastasis...
October 7, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27982511/biochemical-changes-in-the-niche-following-tumor-cell-invasion
#9
A M Decker, F C Cackowski, Y Jung, R S Taichman
Metastatic cancer is the leading cause of all cancer related deaths. Prostate cancer (PCa) metastasizes preferentially to the bone marrow, specifically within the endosteal niche. Endosteal cells secrete homing molecules that may recruit PCa cells to the bone marrow. Once there, the biochemical signature of this niche regulates PCa fate including cellular dormancy or cell cycle arrest, reactivation and resistance to chemotherapeutics. Growth factors, interleukins, adhesion molecules, as well as extra-cellular matrix proteins can collectively change the phenotype of PCa cells...
December 16, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27959896/the-role-of-regulatory-b-cell-like-malignant-cells-and-treg-cells-in-the-mouse-model-of-bcl1-tumor-dormancy
#10
Andrew BitMansour, Laurentiu M Pop, Ellen S Vitetta
Cancer dormancy is a clinical state in which residual tumor cells persist for long periods of time but do not cause detectable disease. In the mouse B cell lymphoma model (BCL1), dormancy can be induced and maintained by immunizing mice with a soluble form of the IgM expressed on the surface of the tumor cells. Immunization induces an anti-idiotype antibody response that maintains dormancy. Mice with dormant tumor have low numbers of BCL1 cells in their spleens that divide and are killed at the same rate. When the anti-Id antibodies wane, the tumor cells grow rapidly and kill the host...
2016: PloS One
https://www.readbyqxmd.com/read/27928096/extremely-late-recurrence-21-years-after-total-removal-of-immature-teratoma-a-case-report-and-literature-review
#11
Yui Mano, Masayuki Kanamori, Toshihiro Kumabe, Ryuta Saito, Mika Watanabe, Yukihiko Sonoda, Teiji Tominaga
Immature teratoma (IMT) is normally treated by resection and adjuvant therapy. The present unusual case of recurrent germinoma occurred 21 years after total resection of pineal IMT. A 3-year-old boy presented with headache, disturbance of consciousness, and Parinaud's syndrome. Magnetic resonance (MR) imaging revealed a pineal mass lesion, and total resection of the tumor was achieved. The histological diagnosis was mature teratoma. He did not receive further treatment, and did well without recurrence for 20 years...
January 15, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/27916615/characterization-of-rare-dormant-and-therapy-resistant-cells-in-acute-lymphoblastic-leukemia
#12
Sarah Ebinger, Erbey Ziya Özdemir, Christoph Ziegenhain, Sebastian Tiedt, Catarina Castro Alves, Michaela Grunert, Michael Dworzak, Christoph Lutz, Virginia A Turati, Tariq Enver, Hans-Peter Horny, Karl Sotlar, Swati Parekh, Karsten Spiekermann, Wolfgang Hiddemann, Aloys Schepers, Bernhard Polzer, Stefan Kirsch, Martin Hoffmann, Bettina Knapp, Jan Hasenauer, Heike Pfeifer, Renate Panzer-Grümayer, Wolfgang Enard, Olivier Gires, Irmela Jeremias
Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD)...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27910972/a-liver-microphysiological-system-of-tumor-cell-dormancy-and-inflammatory-responsiveness-is-affected-by-scaffold-properties
#13
A M Clark, S E Wheeler, C L Young, L Stockdale, J Shepard Neiman, W Zhao, D B Stolz, R Venkataramanan, D Lauffenburger, L Griffith, A Wells
Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells...
December 20, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27896223/urokinase-type-plasminogen-activator-receptor-upar-as-a-new-therapeutic-target-in-cancer
#14
Nunzia Montuori, Ada Pesapane, Francesca W Rossi, Valentina Giudice, Amato De Paulis, Carmine Selleri, Pia Ragno
The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis...
November 2016: Translational Medicine @ UniSa
https://www.readbyqxmd.com/read/27893711/the-induction-of-mig6-under-hypoxic-conditions-is-critical-for-dormancy-in-primary-cultured-lung-cancer-cells-with-activating-egfr-mutations
#15
H Endo, J Okami, H Okuyama, Y Nishizawa, F Imamura, M Inoue
The biologic activity of individual cancer cells is highly heterogeneous. Hypoxia, one of the prominent features of a tumor microenvironment, is thought to be causal in generating this cellular heterogeneity. In this study, we revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. We found that heterodimer formation of the ERBB family receptor tyrosine kinases (RTKs), and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27868104/adaptive-stress-responses-during-tumor-metastasis-and-dormancy
#16
Daniela Senft, Ze Ev A Ronai
To survive inhospitable environments, tumor cells are forced to remodel their signaling pathways by altering transcription, translation, and post-translational modifications. This adaptation is regulated in a spatial and temporal manner and gives rise to individual tumor cells with distinct gene expression and metabolic signatures. Such phenotypic heterogeneity is the result of tumor cell plasticity, which-together with the genetic background of the tumor-determines whether cells resist environmental stress, enter dormancy, or metastasize...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/27819283/axl-is-required-for-tgf-%C3%AE-2-induced-dormancy-of-prostate-cancer-cells-in-the-bone-marrow
#17
Kenji Yumoto, Matthew R Eber, Jingcheng Wang, Frank C Cackowski, Ann M Decker, Eunsohl Lee, Ana Rita Nobre, Julio A Aguirre-Ghiso, Younghun Jung, Russell S Taichman
Disseminated prostate cancer (PCa) cells in the marrow survive for years without evidence of proliferation, while maintaining the capacity to develop into metastatic lesions. These dormant disseminated tumor cells (DTCs) may reside in close proximity to osteoblasts, while expressing high levels of Axl, one of the tyrosine kinase receptors for growth arrest specific 6 (Gas6). Yet how Axl regulates DTC proliferation in marrow remains undefined. Here, we explored the impact of the loss of Axl in PCa cells (PC3 and DU145) on the induction of their dormancy when they are co-cultured with a pre-osteoblastic cell line, MC3T3-E1...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27797969/role-of-the-microenvironment-in-liver-metastasis-from-pre-to-prometastatic-niches
#18
REVIEW
Pnina Brodt
Liver metastases remain a major barrier to successful management of malignant disease, particularly for cancers of the gastrointestinal tract but also for other malignancies, such as breast carcinoma and melanoma. The ability of metastatic cells to survive and proliferate in the liver is determined by the outcome of complex, reciprocal interactions between tumor cells and different local resident subpopulations, including the sinusoidal endothelium, stellate, Kupffer, and inflammatory cells that are mediated through cell-cell and cell-extracellular matrix adhesion and the release of soluble factors...
December 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27784287/induction-of-autophagy-by-arhi-diras3-alters-fundamental-metabolic-pathways-in-ovarian-cancer-models
#19
Argentina Ornelas, Christopher R McCullough, Zhen Lu, Niki M Zacharias, Lindsay E Kelderhouse, Joshua Gray, Hailing Yang, Brian J Engel, Yan Wang, Weiqun Mao, Margie N Sutton, Pratip K Bhattacharya, Robert C Bast, Steven W Millward
BACKGROUND: Autophagy is a bulk catabolic process that modulates tumorigenesis, therapeutic resistance, and dormancy. The tumor suppressor ARHI (DIRAS3) is a potent inducer of autophagy and its expression results in necroptotic cell death in vitro and tumor dormancy in vivo. ARHI is down-regulated or lost in over 60 % of primary ovarian tumors yet is dramatically up-regulated in metastatic disease. The metabolic changes that occur during ARHI induction and their role in modulating death and dormancy are unknown...
October 26, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27761370/the-role-of-hematopoietic-stem-cell-niche-in-prostate-cancer-bone-metastasis
#20
A M Decker, Y Jung, F Cackowski, R S Taichman
Approximately 80% of prostate cancers exhibit some degree of bone metastasis. The role of the bone marrow and the hematopoietic stem cell (HSC) niche in attracting metastatic cells and maintaining dormancy of disseminated tumor cells (DTCs) is an increasingly important topic towards the development of novel prostate cancer therapies. This paper reviews aspects of the HSC niche that lead to prostate cancer cell homing and dormancy in the bone marrow. This review also discusses the role of DTCs in the niche environment and discusses the role of erythropoietin in targeting DTCs within the HSC niche...
September 2016: Journal of Bone Oncology
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