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https://www.readbyqxmd.com/read/29788870/small-molecules-as-drugs-to-upregulate-metastasis-suppressors-in-cancer-cells
#1
Ka Ming Wong, Jiaxing Song, Vasu Saini, Yung H Wong
It is well-recognized that the majority of cancer-related deaths are attributed to metastasis, which can arise from virtually any type of tumor. Metastasis is a complex multistep process wherein cancer cells must break away from the primary tumor, intravasate into the circulatory or lymphatic systems, extravasate, proliferate and eventually colonize secondary sites. Since these molecular processes involve the coordinated actions of numerous proteins, targeted disruptions of key players along these pathways represent possible therapeutic interventions to impede metastasis formation and reduce cancer mortality...
May 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29776156/realizations-of-highly-heterogeneous-collagen-networks-via-stochastic-reconstruction-for-micromechanical-analysis-of-tumor-cell-invasion
#2
Hanqing Nan, Long Liang, Guo Chen, Liyu Liu, Ruchuan Liu, Yang Jiao
Three-dimensional (3D) collective cell migration in a collagen-based extracellular matrix (ECM) is among one of the most significant topics in developmental biology, cancer progression, tissue regeneration, and immune response. Recent studies have suggested that collagen-fiber mediated force transmission in cellularized ECM plays an important role in stress homeostasis and regulation of collective cellular behaviors. Motivated by the recent in vitro observation that oriented collagen can significantly enhance the penetration of migrating breast cancer cells into dense Matrigel which mimics the intravasation process in vivo [Han et al...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29749465/12-s-hete-induces-lymph-endothelial-cell-retraction-in-vitro-by-upregulation-of-sox18
#3
Adryan Fristiohady, Daniela Milovanovic, Sigurd Krieger, Nicole Huttary, Chi Huu Nguyen, Jose Basilio, Walter Jäger, Rainer De Martin, Georg Krupitza
Metastasising breast cancer cells communicate with adjacent lymph endothelia, intravasate and disseminate through lymphatic routes, colonise lymph nodes and finally metastasize to distant organs. Thus, understanding and blocking intravasation may attenuate the metastatic cascade at an early step. As a trigger factor, which causes the retraction of lymph endothelial cells (LECs) and opens entry ports for tumour cell intravasation, MDA-MB231 breast cancer cells secrete the pro-metastatic arachidonic acid metabolite, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(S)-HETE]...
April 26, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29720724/fibroblast-derived-cxcl12-promotes-breast-cancer-metastasis-by-facilitating-tumor-cell-intravasation
#4
Dinesh K Ahirwar, Mohd W Nasser, Madhu M Ouseph, Mohamad Elbaz, Maria C Cuitiño, Raleigh D Kladney, Sanjay Varikuti, Kirti Kaul, Abhay R Satoskar, Bhuvaneswari Ramaswamy, Xiaoli Zhang, Michael C Ostrowski, Gustavo Leone, Ramesh K Ganju
The chemokine CXCL12 has been shown to regulate breast tumor growth, however, its mechanism in initiating distant metastasis is not well understood. Here, we generated a novel conditional allele of Cxcl12 in mice and used a fibroblast-specific Cre transgene along with various mammary tumor models to evaluate CXCL12 function in the breast cancer metastasis. Ablation of CXCL12 in stromal fibroblasts of mice significantly delayed the time to tumor onset and inhibited distant metastasis in different mouse models...
May 3, 2018: Oncogene
https://www.readbyqxmd.com/read/29719259/the-receptor-tyrosine-kinase-axl-is-required-at-multiple-steps-of-the-metastatic-cascade-during-her2-positive-breast-cancer-progression
#5
Marie-Anne Goyette, Stéphanie Duhamel, Léo Aubert, Ariane Pelletier, Paul Savage, Marie-Pier Thibault, Radia Marie Johnson, Peter Carmeliet, Mark Basik, Louis Gaboury, William J Muller, Morag Park, Philippe P Roux, Jean-Philippe Gratton, Jean-François Côté
AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. In the current study, we report AXL expression in HER2-positive (HER2+ ) breast cancers where it correlates with poor patient survival. Using murine models of HER2+ breast cancer, Axl, but not its ligand Gas6, was found to be essential for metastasis. We determined that AXL is required for intravasation, extravasation, and growth at the metastatic site. We found that AXL is expressed in HER2+ cancers displaying epithelial-to-mesenchymal transition (EMT) signatures where it contributes to sustain EMT...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29719241/a-unidirectional-transition-from-migratory-to-perivascular-macrophage-is-required-for-tumor-cell-intravasation
#6
Esther N Arwert, Allison S Harney, David Entenberg, Yarong Wang, Erik Sahai, Jeffrey W Pollard, John S Condeelis
Tumor-associated macrophages (TAMs) are critical for tumor metastasis. Two TAM subsets support cancer cell intravasation: migratory macrophages guide cancer cells toward blood vessels, where sessile perivascular macrophages assist their entry into the blood. However, little is known about the inter-relationship between these functionally distinct TAMs or their possible inter-conversion. We show that motile, streaming TAMs are newly arrived monocytes, recruited via CCR2 signaling, that then differentiate into the sessile perivascular macrophages...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29695547/an-improved-in-vivo-methodology-to-visualise-tumour-induced-changes-in-vasculature-using-the-chick-chorionic-allantoic-membrane-assay
#7
Naside Mangir, Ahtasham Raza, John W Haycock, Christopher Chapple, Sheila Macneil
BACKGROUND/AIM: Decreasing the vascularity of a tumour has proven to be an effective strategy to suppress tumour growth and metastasis. Anti-angiogenic therapies have revolutionized the treatment of advanced-stage cancers, however there is still demand for further improvement. This necessitates new experimental models that will allow researchers to reliably study aspects of angiogenesis. The aim of this study was to demonstrate an in vivo technique in which the highly vascular and accessible chorioallantoic membrane (CAM) of the chick embryo is used to study tumour-induced changes in the macro and microvessels...
May 2018: In Vivo
https://www.readbyqxmd.com/read/29666580/chemical-composition-of-scrophularia-lucida-and-the-effects-on-tumor-invasiveness-in-vitro
#8
Verena Lewenhofer, Lisa Schweighofer, Tobias Ledermüller, Julia Eichsteininger, Hanspeter Kählig, Martin Zehl, Chi H Nguyen, Georg Krupitza, Ali Özmen, Liselotte Krenn
A detannified methanolic extract of Scrophularia lucida L. attenuated the formation of cancer cell-induced circular chemorepellent induced defects (CCIDs) in the lymph endothelial cell barrier, which resemble entry ports for the intravasating tumor into the vasculature as a prerequisite for lymph node metastasis. Therefore, the composition of this extract was studied in an activity-guided approach. Since no data on the secondary metabolites of this plant were available, first phytochemical data were collected in the course of the fractionation of the extract...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29593542/apigenin-and-luteolin-attenuate-the-breaching-of-mda-mb231-breast-cancer-spheroids-through-the-lymph-endothelial-barrier-in-vitro
#9
Junli Hong, Adryan Fristiohady, Chi H Nguyen, Daniela Milovanovic, Nicole Huttary, Sigurd Krieger, Junqiang Hong, Silvana Geleff, Peter Birner, Walter Jäger, Ali Özmen, Liselotte Krenn, Georg Krupitza
Flavonoids, present in fruits, vegetables and traditional medicinal plants, show anticancer effects in experimental systems and are reportedly non-toxic. This is a favorable property for long term strategies for the attenuation of lymph node metastasis, which may effectively improve the prognostic states in breast cancer. Hence, we studied two flavonoids, apigenin and luteolin exhibiting strong bio-activity in various test systems in cancer research and are readily available on the market. This study has further advanced the mechanistic understanding of breast cancer intravasation through the lymphatic barrier...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29590602/ecm-cross-linking-regulates-invadopodia-dynamics
#10
Kamyar Esmaeili Pourfarhangi, Aviv Bergman, Bojana Gligorijevic
Invadopodia are membrane protrusions dynamically assembled by invasive cancer cells in contact with the extracellular matrix (ECM). Invadopodia are enriched by the structural proteins actin and cortactin as well as metalloproteases such as MT1-MMP, whose function is to degrade the surrounding ECM. During metastasis, invadopodia are necessary for cancer cell intravasation and extravasation. Although signaling pathways involved in the assembly and function of invadopodia are well studied, few studies address invadopodia dynamics and how the cell-ECM interactions contribute to cell invasion...
March 27, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29567714/lymph-node-blood-vessels-provide-exit-routes-for-metastatic-tumor-cell-dissemination-in-mice
#11
M Brown, F P Assen, A Leithner, J Abe, H Schachner, G Asfour, Z Bago-Horvath, J V Stein, P Uhrin, M Sixt, D Kerjaschki
During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels...
March 23, 2018: Science
https://www.readbyqxmd.com/read/29565466/single-nucleotide-variant-profiles-of-viable-single-circulating-tumour-cells-reveal-ctc-behaviours-in-breast-cancer
#12
Yipeng Wang, Liping Guo, Lin Feng, Wen Zhang, Ting Xiao, Xuebing Di, Guoji Chen, Kaitai Zhang
Circulating tumour cell (CTC) behaviours are distinct from those of bulk tissues. Thus, treatments to eliminate CTCs differ from the regimens followed to reduce the primary tumour and its metastases. Accordingly, comprehensively deciphering the single nucleotide variant (SNV) profiles in CTCs, which partially determine CTC behaviours, is a priority. Using viable CTCs isolated with the oHSV1‑hTERT‑GFP virus coupled with fluorescence‑activated cell sorting (FACS), the whole genome was amplified using the multiple annealing and looping‑based amplification cycle (MALBAC) method...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29561794/microfabrication-based-three-dimensional-3-d-extracellular-matrix-microenvironments-for-cancer-and-other-diseases
#13
REVIEW
Kena Song, Zirui Wang, Ruchuan Liu, Guo Chen, Liyu Liu
Exploring the complicated development of tumors and metastases needs a deep understanding of the physical and biological interactions between cancer cells and their surrounding microenvironments. One of the major challenges is the ability to mimic the complex 3-D tissue microenvironment that particularly influences cell proliferation, migration, invasion, and apoptosis in relation to the extracellular matrix (ECM). Traditional cell culture is unable to create 3-D cell scaffolds resembling tissue complexity and functions, and, in the past, many efforts were made to realize the goal of obtaining cell clusters in hydrogels...
March 21, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29520361/beyond-enumeration-functional-and-computational-analysis-of-circulating-tumor-cells-to-investigate-cancer-metastasis
#14
REVIEW
Francesc Castro-Giner, Manuel C Scheidmann, Nicola Aceto
Circulating tumor cells (CTCs) are defined as those cells that detach from a cancerous lesion and enter the bloodstream. While generally most CTCs are subjected to high shear stress, anoikis signals, and immune attack in the circulatory system, few are able to survive and reach a distant organ in a viable state, possibly leading to metastasis formation. A large number of studies, both prospective and retrospective, have highlighted the association between CTC abundance and bad prognosis in patients with various cancer types...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29444699/the-hyster-study-the-effect-of-intracervically-administered-terlipressin-versus-placebo-on-the-number-of-gaseous-emboli-and-fluid-intravasation-during-hysteroscopic-surgery-study-protocol-for-a-randomized-controlled-clinical-trial
#15
Lucilla E Overdijk, Bart M P Rademaker, Paul J M van Kesteren, Peter de Haan, Robert K Riezebos, Oscar C H Haude
BACKGROUND: Transcervical resection of myoma or endometrium is a safe, hysteroscopic, minimally invasive procedure. However, intravasation of distension fluid is a common phenomenon during these procedures. In a previous study we observed venous gas emboli in almost every patient. The severity of hysteroscopic-derived embolization has been shown to be correlated to the amount of intravasation. In addition, paradoxical gas embolism, which is potentially dangerous, was observed in several patients...
February 14, 2018: Trials
https://www.readbyqxmd.com/read/29416682/mechanism-of-action-and-efficacy-of-ly2109761-a-tgf-%C3%AE-receptor-inhibitor-targeting-tumor-microenvironment-in-liver-cancer-after-tace
#16
Xiaojun He, Xiaopeng Guo, Hongsen Zhang, Xiangchuang Kong, Fan Yang, Chuansheng Zheng
TACE (transcatheter arterial chemoembolization) has been recognized as an effective palliative treatment option for patients with HCC, however, the medium-long term efficacy of it remains modest. LY2109761, a TGF-β receptor inhibitor, was confirmed to reduce tumor cell growth, intravasation, and metastatic dissemination of HCC cells through different molecular mechanisms. This study aims to investigate the treatment effect of combining TACE therapy with LY2109761- a TGF-β receptor I kinase inhibitor on suppressing tumor growth and metastasis in a rabbit VX2 tumor model...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29402936/microscale-gene-expression-analysis-of-tumor-associated-macrophages
#17
Kuldeep S Attri, Kamiya Mehla, Surendra K Shukla, Pankaj K Singh
Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348457/ltbp3-promotes-early-metastatic-events-during-cancer-cell-dissemination
#18
Elena I Deryugina, Ewa Zajac, Lior Zilberberg, Tomoki Muramatsu, Grishma Joshi, Branka Dabovic, Daniel Rifkin, James P Quigley
Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are important for the secretion, activation, and function of mature TGFβ, especially so in cancer cell physiology. However, specific roles of the LTBPs remain understudied in the context of the primary tumor microenvironment. Herein, we investigated the role of LTBP3 in the distinct processes involved in cancer metastasis. By using three human tumor cell lines of different tissue origin (epidermoid HEp-3 and prostate PC-3 carcinomas and HT-1080 fibrosarcoma) and several metastasis models conducted in both mammalian and avian settings, we show that LTBP3 is involved in the early dissemination of primary cancer cells, namely in the intravasation step of the metastatic cascade...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29334196/microfluidic-tumor-vascular-model-to-study-breast-cancer-cell-invasion-and-intravasation
#19
Supriya Nagaraju, Danh Truong, Ghassan Mouneimne, Mehdi Nikkhah
Cancer is a major leading cause of disease-related death in the world. The severe impact of cancer can be attributed to poor understanding of the mechanisms involved in earliest steps of the metastatic cascade, specifically invasion into the surrounding stroma and intravasation into the blood capillaries. However, conducting integrated biological studies of invasion and intravasation have been challenging, within in vivo models and traditional in vitro assay, due to difficulties in establishing a precise tumor microenvironment...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29307118/chemotherapy-induced-metastasis-mechanisms-and-translational-opportunities
#20
George S Karagiannis, John S Condeelis, Maja H Oktay
Tumors often overcome the cytotoxic effects of chemotherapy through either acquired or environment-mediated drug resistance. In addition, signals from the microenvironment obfuscate the beneficial effects of chemotherapy and may facilitate progression and metastatic dissemination. Seminal mediators in chemotherapy-induced metastasis appear to be a wide range of hematopoietic, mesenchymal and immune progenitor cells, originating from the bone marrow. The actual purpose of these cells is to orchestrate the repair response to the cytotoxic damage of chemotherapy...
January 6, 2018: Clinical & Experimental Metastasis
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