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vascular mimicry

T Azad, H J Janse van Rensburg, E D Lightbody, B Neveu, A Champagne, A Ghaffari, V R Kay, Y Hao, H Shen, B Yeung, B A Croy, K L Guan, F Pouliot, J Zhang, C J B Nicol, X Yang
The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ...
March 13, 2018: Nature Communications
Nipaporn Ngernyuang, Rong Shao, Komsun Suwannarurk, Temduang Limpaiboon
Vasculogenic mimicry (VM) is an alternative microvascular system which tumour cells orchestrate, independent of endothelial cell-mediated angiogenesis. VM develops tumour vascular networks that correlate with tumour growth, metastasis, and short survival time of patients with a number of cancers. However, little is known regarding VM in the vascularisation of cervical cancer. Chitinase 3 like 1 (CHI3L1) has been previously reported to display the ability to induce angiogenesis in cervical cancer. Here, we explored a pathological role of CHI3L1 in tumour cell-mediated vascularisation...
February 13, 2018: Pathology
Qing-Shan Wang, Rui He, Fan Yang, Li-Juan Kang, Xiao-Qing Li, Li Fu, Baocun Sun, Yu-Mei Feng
Lymphatic metastasis is the main route of breast cancer metastasis. It is known that lymphangiogenesis facilitates lymphatic metastasis through vascular endothelial growth factor-C (VEGF-C)/VEGF receptor 3 (VEGFR3) pathway-linked interactions between the tumor and its microenvironment. Here, we report a novel mechanism of lymphatic metastasis by which aggressive basal-like breast cancer (BLBC) cells form lymphatic vessel-like structures that are identified by the positive expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin, and VEGFR3, and termed as lymphangiogenic mimicry (LM), for the first time...
January 30, 2018: Cancer Letters
Soussan Irani, Arash Dehghan
Objectives: Mucoepidermoid carcinoma (MEC) accounts for 35% of all malignant salivary gland tumors. Previous investigations have shown that vasculogenic mimicry (VM) exists in many cancers which can be used as a prognostic factor of poor prognosis. Elevated expression level of vascular endothelial (VE)-cadherin has been implicated in cancer neovascularization, growth, and progression. The current study aimed to study the presence of VE-cadherin in VM channels and tumor cells in different grades of MEC...
November 2017: Journal of International Society of Preventive & Community Dentistry
Qiaoge Zhang, Ge Song, Lili Yao, Yankun Liu, Min Liu, Shengping Li, Hua Tang
BACKGROUND: Hepatitis B virus (HBV) plays a critical role in the tumorigenic behavior of human hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to participate in HCC development via the regulation of their target genes. However, HBV-modulated miRNAs involved in tumorigenesis remain to be identified. Here, we found that a novel highly expressed miRNA, TLRC-m0008_3p (miR-3928v), may be an important factor that promotes the malignancy of HBV-related HCC. METHODS: Solexa sequencing was applied to profile miRNAs, and RT-qPCR was used to identify and quantitate miRNAs...
January 29, 2018: Journal of Experimental & Clinical Cancer Research: CR
Khaled Greish, Anfal Jasim, Neha Parayath, Sara Abdelghany, Ali Alkhateeb, Sebastien Taurin, Hayley Nehoff
Glioblastoma multiforme (GBM) defies the currently practiced management of radiotherapy, chemotherapy and surgery and hence, it is associated with a high fatality rate with a median survival of 14.6 months. In our previous work investigating different tyrosine kinase inhibitors (TKIs), we established that a combination of Crizotinib and Dasatinib exerted the most potent effect on different GBM cell lines. In the current work, to improve targeted therapy at the site of the tumor and avoid systemic toxicity, we exploited the enhanced permeability and retention effect by designing micellar formulations of these two TKIs...
December 18, 2017: Journal of Drug Targeting
Daniela Trisciuoglio, Maria Grazia Tupone, Marianna Desideri, Marta Di Martile, Chiara Gabellini, Simonetta Buglioni, Matteo Pallocca, Gabriele Alessandrini, Simona D'Aguanno, Donatella Del Bufalo
By using human melanoma and glioblastoma cell lines and their derivative BCL-XL overexpressing clones, we investigated the role of BCL-XL in aggressive features of these two tumor histotypes. We found that in both models, BCL-XL overexpression increased in vitro cell migration and invasion and facilitated tumor cells to form de novo vasculogenic structures. Furthermore, BCL-XL overexpressing cells exhibited higher tumors sphere formation capacity and expressed higher levels of some stem cell markers, supporting the concept that BCL-XL plays essential roles in the maintenance of cancer stem cell phenotype...
December 13, 2017: Cell Death & Disease
Shuixian Li, Qianyun Zhang, Lichun Zhou, Yanhui Guan, Shang Chen, Yu Zhang, Xiuzhen Han
Breast cancer is one of the most serious malignant tumors that harm to women's health. Vasculogenic mimicry (VM) is an alternative type of blood supplement independent of endothelial vessels, which refers to the formation of tumor cell-lined vessels and is associated with tumor invasion, metastasis and poor cancer patient prognosis. Prior antiangiogenic therapy just focused on vascular endothelial cells and did not significantly affect VM. DMBT, 6, 6'-bis (2, 3-dimethoxybenzoyl)-a, a-D-trehalose, has shown to have multiple anti-tumor invasion and metastasis activities; however the exact mechanism is not thoroughly elucidated...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
A Villasante, K Sakaguchi, J Kim, N K Cheung, M Nakayama, H Parsa, T Okano, T Shimizu, G Vunjak-Novakovic
Neuroblastoma is a vascularized pediatric tumor derived from neural crest stem cells that displays vasculogenic mimicry and can express a number of stemness markers, such as SOX2 and NANOG. Tumor relapse is the major cause of succumbing to this disease, and properties attributed to cancer stem-like cells (CSLC), such as drug-resistance and cell plasticity, seem to be the key mechanisms. However, the lack of controllable models that recapitulate the features of human neuroblastoma limits our understanding of the process and impedes the development of new therapies...
2017: Theranostics
Dae-Geun Song, Gyu-Ho Lee, Seo Hee Nam, Jin-Gyu Cheong, Doyoung Jeong, Seo-Jin Lee, Cheol-Ho Pan, Jae Woo Jung, Hye-Jin Kim, Jihye Ryu, Ji Eon Kim, Somi Kim, Chang Yun Cho, Min-Kyung Kang, Kyung-Min Lee, Jung Weon Lee
Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocellular carcinoma tissues and enhances migration in two-dimensional environments. Here, we investigated how TM4SF5 is involved in diverse pro-metastatic phenotypes in in vivo-like three-dimensional (3D) extracellular matrix gels. TM4SF5-positive cells aggressively formed invasive foci in 3D Matrigel, depending on TM4SF5-mediated signaling activity, cytoskeletal organization, and matrix metallopeptidase (MMP) 2-mediated extracellular remodeling, whereas TM4SF5-null cells did not...
October 13, 2017: Oncotarget
Xing Guo, Shugang Xu, Xiao Gao, Jian Wang, Hao Xue, Zihang Chen, Jinsen Zhang, Xiaofan Guo, Mingyu Qian, Wei Qiu, Gang Li
Macrophage migration inhibitory factor (MIF) is over-expressed and secreted in various cancer cells in particular in response to hypoxia. Recent studies have shown that, under hypoxic conditions, glioblastoma (GBM) cells display the ability to drive blood-perfused vasculogenic mimicry (VM). The aim of this study was to investigate the underlying mechanism of MIF in the regulation of hypoxia-induced VM in GBM cells. By analyzing clinical specimens, we observed the co-localization of MIF, C-X-C motif chemokine receptor 4 (CXCR4) and VM in hypoxic regions of gliomas...
October 6, 2017: Oncotarget
Ana Cavaco, Maryam Rezaei, Stephan Niland, Johannes A Eble
After oncogenic transformation, tumor cells rewire their metabolism to obtain sufficient energy and biochemical building blocks for cell proliferation, even under hypoxic conditions. Glucose and glutamine become their major limiting nutritional demands. Instead of being autonomous, tumor cells change their immediate environment not only by their metabolites but also by mediators, such as juxtacrine cell contacts, chemokines and other cytokines. Thus, the tumor cells shape their microenvironment as well as induce resident cells, such as fibroblasts and endothelial cells (ECs), to support them...
November 7, 2017: International Journal of Molecular Sciences
Emily Pulford, James McEvoy, Ashleigh Hocking, Sarita Prabhakaran, Kim Griggs, Sonja Klebe
Malignant mesothelioma (MM) is an aggressive malignancy of the serosal membranes, with poor overall survival and quality of life. Limited targeted treatment strategies exist due to restricted knowledge of pathogenic pathways. Vasculogenic mimicry (VM) is a newly described phenomenon associated with increased aggressiveness in other malignancies, and has been characterized in MM. Normal mesothelium expresses aquaporin 1 (AQP1) and retained expression has been associated with improved survival in MM. AQP1 is expressed by normal vascular endothelium and is involved in mediating MM cell motility and proliferation...
November 1, 2017: International Journal of Molecular Sciences
E M Langer, N D Kendsersky, C J Daniel, G M Kuziel, C Pelz, K M Murphy, M R Capecchi, R C Sears
During normal tumor growth and in response to some therapies, tumor cells experience acute or chronic deprivation of nutrients and oxygen and induce tumor vascularization. While this occurs predominately through sprouting angiogenesis, tumor cells have also been shown to directly contribute to vessel formation through vascular mimicry (VM) and/or endothelial transdifferentiation. The extrinsic and intrinsic mechanisms underlying tumor cell adoption of endothelial phenotypes, however, are not well understood...
October 30, 2017: Oncogene
Julie-Ann Hulin, Sara Tommasi, David Elliot, Dong Gui Hu, Benjamin C Lewis, Arduino A Mangoni
Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is responsible for metabolism of an endogenous inhibitor of nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), which plays a key role in modulating angiogenesis. In addition to angiogenesis, tumours can establish a vascular network by forming vessel-like structures from tumour cells; a process termed vasculogenic mimicry (VM). Here, we identified over-expression of DDAH1 in aggressive MDA-MB-231, MDA-MB-453 and BT549 breast cancer cell lines when compared to normal mammary epithelial cells...
October 25, 2017: Scientific Reports
Wei Xue, Xuesong Du, Hao Wu, Heng Liu, Tian Xie, Haipeng Tong, Xiao Chen, Yu Guo, Weiguo Zhang
Glioblastoma (GBM) is a highly angiogenic malignancy, and its abundant, aberrant neovascularization is closely related to the proliferation and invasion of tumor cells. However, anti-angiogenesis combined with standard radio-/chemo-therapy produces little improvement in treatment outcomes. Determining the reason for treatment failure is pivotal for GBM treatment. Here, histopathological analysis and dynamic contrast-enhanced MRI (DCE-MRI) were used to explore the effects of temozolomide (TMZ) and bevacizumab (BEV) on GBM neovascularization patterns in an orthotopic U87MG mouse model at 1, 3 and 6 days after treatment...
October 24, 2017: Scientific Reports
Mingqi Qu, Ju Yu, Hongyuan Liu, Ying Ren, Chunxiao Ma, Xingyao Bu, Qing Lan
Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed...
October 2017: Molecules and Cells
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
September 15, 2017: Oncotarget
(no author information available yet)
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 10 more questions are presented as followed. Question 57. What are the major stresses that drive the formation, progression, and metastasis of a cancer? Question 58. What is the mechanism responsible for altering an acidic intracellular pH and a basic extracellular pH in normal tissue cells to a basic intracellular pH and an acidic extracellular pH in cancer cells, a fundamental and yet largely ignored phenomenon? Question 59...
October 3, 2017: Chinese Journal of Cancer
Jinah Jang
Numerous microfabrication approaches have been developed to recapitulate morphologically and functionally organized tissue microarchitectures in vitro; however, the technical and operational limitations remain to be overcome. 3D printing technology facilitates the building of a construct containing biomaterials and cells in desired organizations and shapes that have physiologically relevant geometry, complexity, and micro-environmental cues. The selection of biomaterials for 3D printing is considered one of the most critical factors to achieve tissue function...
August 18, 2017: Bioengineering
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