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Lymphatic endothelial cells

Zacharias Kontarakis, Andrea Rossi, Sophie Ramas, Michael T Dellinger, Didier Y R Stainier
Organ homeostasis relies upon cellular and molecular processes that restore tissue structure and function in a timely fashion. Lymphatic vessels help maintain fluid equilibrium by returning interstitial fluid that evades venous uptake back to the circulation. Despite its important role in tissue homeostasis, cancer metastasis, and close developmental origins with the blood vasculature, the number of molecular players known to control lymphatic system development is relatively low. Here we show, using genetic approaches in zebrafish and mice, that the endothelial specific microRNA mir-126, previously implicated in vascular integrity, regulates lymphatic development...
March 14, 2018: Developmental Biology
Erika Gucciardo, Sirpa Loukovaara, Ani Korhonen, Pauliina Repo, Beatriz Martins, Helena Vihinen, Eija Jokitalo, Kaisa Lehti
Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady-state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions...
March 13, 2018: Journal of Pathology
Katsuhiro Nakagawa, Takanori Matsuki, Liang Zhao, Kanako Kuniyoshi, Hiroki Tanaka, Isao Ebina, Kenta J Yoshida, Hiroshi Nabeshima, Kiyoharu Fukushima, Hisashi Kanemaru, Fumihiro Yamane, Takahiro Kawasaki, Tomohisa Machida, Hisamichi Naito, Nobuyuki Takakura, Takashi Satoh, Shizuo Akira
Schlafen-8 (Slfn8) is a member of the Schlafen family of proteins, which harbor helicase domains and are induced by LPS and interferons. It has been reported that the Schlafen family are involved in various cellular functions, including proliferation, differentiation and regulation of virus replication. Slfn8 has been implicated in T-cell differentiation in the thymus. However, the roles of Slfn8 in the immune system remains unclear. In this study, we generated Slfn8 knockout mice (Slfn8-/-) and investigated the immunological role of Slfn8 using the T-cell-mediated autoimmune model experimental autoimmune encephalomyelitis (EAE)...
March 8, 2018: International Immunology
Anke Schlüter, Patrick Weller, Oliver Kanaan, Ivonne Nel, Lukas Heusgen, Benedikt Höing, Pia Haßkamp, Sebastian Zander, Magis Mandapathil, Nina Dominas, Judith Arnolds, Boris A Stuck, Stephan Lang, Agnes Bankfalvi, Sven Brandau
BACKGROUND: Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients...
March 9, 2018: BMC Cancer
Athanasia Bletsa, Hisham Abdalla, Sigbjørn Løes, Ellen Berggreen
BACKGROUND: The lymphatic growth factors vascular endothelial growth factor (VEGF) -C and -D are important for maintenance and growth of lymphatic vessels (lymphangiogenesis), but their localization in human gingiva is unknown. This study investigated the expression of VEGF-C and -D in human gingiva and isolated human gingival fibroblasts (HGFs). In addition, the localization of their main receptor VEGFR-3 was explored. METHODS: Non-inflamed gingiva from 6 donors was used for immunohistochemistry or isolation of HGFs...
February 19, 2018: Journal of Periodontology
Javier R Jaldin-Fincati, Rafaela V S Pereira, Philip J Bilan, Amira Klip
Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic (HDLEC) and blood (HAMEC) origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor (IR) and signal in response to insulin as low as 2...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Chieh-Lung Cheng, Yung-Cheng Su, Tsu-Yi Chao, Chung-Wu Lin, Sheng-Chieh Chou, Ming Yao, Sung-Hsin Kuo, Shan-Chi Yu
Intralymphatic spread is common in solid cancers, but has been rarely studied in lymphomas. Review of 635 extranodal specimens from 475 diffuse large B-cell lymphoma (DLBCL) patients revealed intralymphatic spread in 10 surgical resection specimens from 10 patients including 9 de novo DLBCLs and 1 Richter transformation. The prevalence in de novo DLBCL with extranodal involvements was 1.65%. The most common involved site of intralymphatic spread was the gastrointestinal tract, followed by the female genital tract and breasts...
March 2, 2018: American Journal of Surgical Pathology
Jie Yang, Siya Zhang, Lingyun Zhang, Xiaoping Xie, Hui Wang, Zuliang Jie, Meidi Gu, Jin-Young Yang, Xuhong Cheng, Shao-Cong Sun
B cells home to the lymph nodes (LNs) via high endothelial venules (HEVs) under the guidance of chemokines, particularly CXCL13. However, as CXCL13 is not directly made in HEVs, the molecular mechanism mediating B-cell homing to LNs has remained unclear. We show here that nuclear factor (NF)-κB-inducing kinase (NIK), a kinase mediating activation of the noncanonical NF-κB pathway, functions in lymphatic endothelial cells (LECs) to regulate B-cell homing to LNs. LEC-conditional deletion of NIK in mice did not affect the integrity or global function of lymphatic vessels but caused a severe reduction in the frequency of B cells in LNs...
March 5, 2018: Cellular & Molecular Immunology
Manu Beerens, Xabier L Aranguren, Benoit Hendrickx, Wouter Dheedene, Tom Dresselaers, Uwe Himmelreich, Catherine Verfaillie, Aernout Luttun
Lymphatic capillary growth is an integral part of wound healing, yet, the combined effectiveness of stem/progenitor cells on lymphatic and blood vascular regeneration in wounds needs further exploration. Stem/progenitor cell transplantation also emerged as an approach to cure lymphedema, a condition caused by lymphatic system deficiency. While lymphedema treatment requires lymphatic system restoration from the capillary to the collector level, it remains undetermined whether stem/progenitor cells support a complex regenerative response across the entire anatomical spectrum of the system...
March 1, 2018: Scientific Reports
Khushbu Rauniyar, Sawan Kumar Jha, Michael Jeltsch
Because virtually all tissues contain blood vessels, the importance of hemevascularization has been long recognized in regenerative medicine and tissue engineering. However, the lymphatic vasculature has only recently become a subject of interest. Central to the task of growing a lymphatic network are lymphatic endothelial cells (LECs), which constitute the innermost layer of all lymphatic vessels. The central molecule that directs proliferation and migration of LECs during embryogenesis is vascular endothelial growth factor C (VEGF-C)...
2018: Frontiers in Bioengineering and Biotechnology
Sze Chuen Cesar Wong, Moon Tong Cheung, Lewis Lai Yin Luk, Vivian Ha Man Lee, Pak Tat Chan, Hin Fung Andy Tsang, Evelyn Yin Kwan Wong, Vivian Weiwen Xue, Amanda Kit Ching Chan, John Kwok Cheung Chan
BACKGROUND: Cytokeratin 20-positive cells in lymph nodes from pN0 colorectal cancer (CRC) patients were detected previously by us. The aims of this study were to investigate which tumor metastasis-related genes were involved and their potential clinical significance. RESULTS: Fourteen of 84 (17%) genes were differentially expressed by at least 2-fold. Among them, 10 genes were up-regulated whereas 4 genes were down-regulated. Those differential expressed genes were validated in the second cohort of specimens...
January 23, 2018: Oncotarget
Mark W Majesky
The vascular system forms as a branching network of endothelial cells that acquire identity as arterial, venous, hemogenic, or lymphatic. Endothelial specification depends on gene targets transcribed by Ets domain-containing factors, including Ets variant gene 2 (Etv2), together with the activity of chromatin-remodeling complexes containing Brahma-related gene-1 (Brg1). Once specified and assembled into vessels, mechanisms regulating lumen diameter and axial growth ensure that the structure of the branching vascular network matches the need for perfusion of target tissues...
March 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Padam Parmar, Nisha Marwah, Sanjeev Parshad, Taruna Yadav, Ashima Batra, Rajeev Sen
Various studies have demonstrated that the lymphatic system is the additional route for solid tumor metastasis. Lymph nodes metastasis in Head and neck squamous cell carcinoma (HNSCC) is a major prognostic indicator for disease progression and a guide for therapeutic strategies. We conducted a study to compare intratumoral (IT) and peritumoral (PT) lymphatic vessel density (LVD) in HNSCC using lymphatic marker D2-40 and its correlation with lymph node metastasis, histological grading and other clinicopathological parameters...
March 2018: Indian Journal of Otolaryngology and Head and Neck Surgery
Marta Unolt, Jessica Barry, Maria Cristina Digilio, Bruno Marino, Anne Bassett, Erwin Oechslin, David W Low, Jean B Belasco, Staci Kallish, Kathleen Sullivan, Elaine H Zackai, Donna M McDonald-McGinn
BACKGROUND: Lymphedema is an abnormal accumulation of interstitial fluid within the tissues. Primary lymphedema is caused by aberrant lymphangiogenesis and it has been historically classified based on age at presentation. Although most cases are sporadic, primary lymphedema may be familial or present in association with chromosomal abnormalities and syndromic disorders. To the best of our knowledge, primary lymphedema has never been described in patients with 22q11.2 deletion syndrome...
February 12, 2018: European Journal of Medical Genetics
Xin Zhang, Hesheng Luo
Lymphatic and hematogenous spread are the most common ways for tumors to metastasize. Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) particularly VEGF-A is important in the process of angiogenesis. The current research has indicated that thalidomide (THD) may be able to inhibit angiogenesis, stimulate the activity of the immune system and inhibit the adherence of cancer cells to stromal cells. These changes may lead to suppression of tumor occurrence and development...
March 2018: Oncology Letters
Sooeun Oh, Minkoo Seo, Jun-Sub Choi, Choun-Ki Joo, Suk Kyeong Lee
Discoidin domain receptor 1 (DDR1) is involved in tumorigenesis and angiogenesis. However, its role in lymphangiogenesis has been unknown. Here, we tested whether downregulation of DDR1 expression by miR-199a/b can suppress lymphangiogenesis. We also aimed to identify miRNA target site(s) in the 3' untranslated region (UTR) of DDR1 . Transfection with miR-199a/b-5p mimics reduced expression of DDR1 and tube formation in primary human dermal lymphatic endothelial cells, whereas miR-199a/b-5p inhibitors showed the opposite effects...
February 28, 2018: Molecules and Cells
Qi Xie, Xiaocui Chen, Yinghua Xu, Jing Liang, Fufang Wang, Ju Liu
Tube formation is one of the fundamental events required by angiogenesis and lymphangiogenesis. To date, there is little knowledge on the effects of hypoxia on tube formation of human dermal lymphatic endothelial cells (HDLECs). In this study, we found that tube formation of HDLECs was inhibited under hypoxic condition with decreased expressions of VEGF-D, CEACAM1 and Prox1 genes. However, hypoxia-induced inhibition of tube formation of HDLECs was reversed by conditional media from hypoxic tumor cells. After knockdown of CEACAM1 by siRNA transfection, tube formation of HDLECs was increased with elevated Prox1 expression, suggesting that CEACAM1 downregulates Prox1 and plays an inhibitory role in tube formation of HDLECs...
February 7, 2018: Cellular Signalling
David G Jackson
LYVE-1, a close relative of the leucocyte receptor, CD44, is the main receptor for hyaluronan (HA) in lymphatic vessel endothelium and a widely used marker for distinguishing between blood and lymphatic vessels. Enigmatic for many years because of its anomalous HA-binding characteristics, the function of LYVE-1 has just recently been identified as that of a lymphatic docking receptor for dendritic cells, selectively engaging with their surface HA glycocalyx to regulate entry to peripheral lymphatics and migration to downstream lymph nodes for immune activation...
February 6, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Deepa A G, Bindu Janardanan-Nair, Varun B R
Background: Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is specifically expressed in lymphatic endothelial cells. Studies have shown that assessment of podoplanin expression in the epithelial cells can be used to predict the malignant transformation of potentially malignant disorders and the metastatic tendency of primary head and neck squamous cell carcinoma. The aim of our study was to compare the expression of podoplanin in oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma with that in normal buccal mucosa by immunohistochemical methods...
December 2017: Journal of Clinical and Experimental Dentistry
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
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