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Lymphatic endothelial cell

Hao Wu, H N Ashiqur Rahman, Yunzhou Dong, Xiaolei Liu, Yang Lee, Aiyun Wen, Kim Ht To, Li Xiao, Amy E Birsner, Lauren Bazinet, Scott Wong, Kai Song, Megan L Brophy, M Riaj Mahamud, Baojun Chang, Xiaofeng Cai, Satish Pasula, Sukyoung Kwak, Wenxia Yang, Joyce Bischoff, Jian Xu, Diane R Bielenberg, J Brandon Dixon, Robert J D'Amato, R Sathish Srinivasan, Hong Chen
Impaired lymphangiogenesis is a complication of chronic complex diseases, including diabetes. VEGF-C/VEGFR3 signaling promotes lymphangiogenesis, but how this pathway is affected in diabetes remains poorly understood. We previously demonstrated that loss of epsins 1 and 2 in lymphatic endothelial cells (LECs) prevented VEGF-C-induced VEGFR3 from endocytosis and degradation. Here, we report that diabetes attenuated VEGF-C-induced lymphangiogenesis in corneal micropocket and Matrigel plug assays in WT mice but not in mice with inducible lymphatic-specific deficiency of epsins 1 and 2 (LEC-iDKO)...
August 13, 2018: Journal of Clinical Investigation
Qiaoli Ma, Lothar C Dieterich, Kristian Ikenberg, Samia B Bachmann, Johanna Mangana, Steven T Proulx, Valerie C Amann, Mitchell P Levesque, Reinhard Dummer, Peter Baluk, Donald M McDonald, Michael Detmar
Tumor lymphangiogenesis is accompanied by a higher incidence of sentinel lymph node metastasis and shorter overall survival in several types of cancer. We asked whether tumor lymphangiogenesis might also occur in distant organs with established metastases and whether it might promote further metastatic spread of those metastases to other organs. Using mouse metastasis models, we found that lymphangiogenesis occurred in distant lung metastases and that some metastatic tumor cells were located in lymphatic vessels and draining lymph nodes...
August 2018: Science Advances
Gui-Li Yang, Lu-Yuan Li
Vascular hyperpermeability occurs in angiogenesis and several pathobiological conditions, producing elevated interstitial fluid pressure and lymphangiogenesis. How these closely related events are modulated is a fundamentally important question regarding the maintenance of vascular homeostasis and treatment of disease conditions such as cancer, stroke, and myocardial infarction. Signals mediated by vascular endothelial growth factor receptors, noticeably VEGFR-1, -2, and -3, are centrally involved in the promotion of both blood vessel and lymphatic vessel growth...
2018: Signal Transduction and Targeted Therapy
Karen M Watters, Preety Bajwa, Hilary A Kenny
Ovarian cancer progression involves multifaceted and variable tumor microenvironments (TMEs), from the in situ carcinoma in the fallopian tube or ovary to dissemination into the peritoneal cavity as single cells or spheroids and attachment to the mesothelial-lined surfaces of the omentum, bowel, and abdominal wall. The TME comprises the tumor vasculature and lymphatics (including endothelial cells and pericytes), in addition to mesothelial cells, fibroblasts, immune cells, adipocytes and extracellular matrix (ECM) proteins...
August 9, 2018: Cancers
Yoshikazu Furusawa, Shinji Yamada, Shunsuke Itai, Takuro Nakamura, Masato Fukui, Hiroyuki Harada, Mika K Kaneko, Yukinari Kato
Rat podoplanin (rPDPN) is a recognized lymphatic endothelial cell marker and is expressed on the podocytes of kidney and type I lung alveolar cells. rPDPN is a type I transmembrane sialoglycoprotein and induces platelet aggregation via the C-type lectin-like receptor-2 of platelets. It comprises four platelet aggregation-stimulating (PLAG) domains: PLAG1-3, present in the N-terminus, and PLAG4, in the center of the PDPN protein. Previously, we developed a mouse anti-rPDPN monoclonal antibody clone, PMab-2, by immunizing the PLAG2 and PLAG3 domains of rPDPN...
August 8, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Hong Jun Kim, Min Jee Jo, Bo Ram Kim, Jung Lim Kim, Yoon A Jeong, Yoo Jin Na, Seong Hye Park, Suk-Young Lee, Dae-Hee Lee, Baek-Hui Kim, Young Do Yoo, Sang Cheul Oh
Introduction: Reactive oxygen species modulator-1 (Romo1) is a protein that modulates levels of reactive oxygen species (ROS) and has been reported to affect cancer cell invasion and proliferation via persistent inflammation. Several studies have demonstrated the clinical application of Romo1 as a prognostic marker in non-small cell lung cancer (NSCLC); however, there have been no studies investigating the mechanism by which Romo1 adversely affects the prognosis of these patients. Methods: We examined Romo1, ROS, and vascular endothelial growth factor (VEGF) in tumor tissues immunohistochemically...
2018: OncoTargets and Therapy
Heon-Woo Lee, Pengchun Yu, Michael Simons
The blood and lymphatic vasculatures are vital to the maintenance of homeostasis. The interaction between two vascular networks throughout the body is precisely controlled to enable oxygen and nutrient delivery, removal of carbon dioxide and metabolic waste, drainage of interstitial fluid, transport of immune cells, and other key activities. Recent years have seen an explosion of information dealing with the development and function of the lymphatic system. The growth of lymphatic vessels, termed lymphangiogenesis, is a high-energy requirement process that involves sprouting, proliferation, migration, and remodeling of lymphatic endothelial cells and capillaries...
2018: F1000Research
Pengfei Pang, Xiaojun Hu, Bin Zhou, Junjie Mao, Yu Liang, Zaibo Jiang, Mingsheng Huang, Ruihong Liu, Youyong Zhang, Jiesheng Qian, Junsong Liu, Jinxin Xu, Yaqin Zhang, Maoheng Zu, Yiming Wang, Huanhuan He, Hong Shan
Vascular malformations present diagnostic and treatment challenges. In particular, malformations of vessels to the viscera are often diagnosed late or incorrectly due to an insidious onset and deep location of the disease. Therefore, a better knowledge of the genetic mutations underlying such diseases is needed. Here we evaluated a four-generation family carrying vascular malformations of major vessels that affect multiple organs, which we named multi-organ venous and lymphatic defect syndrome (MOVLD). Genetic analyses identified an association between a mutation in DDX24 - a gene for which the function is largely unknown - and MOVLD...
July 31, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yuta Hara, Ryota Torii, Shiho Ueda, Erina Kurimoto, Eri Ueda, Hiroshi Okura, Yutaka Tatano, Hideki Yagi, Yoshiya Ohno, Toshiyuki Tanaka, Kazue Masuko, Takashi Masuko
Although cancer metastasis is associated with a poor prognosis, the mechanisms of this event, especially via lymphatic vessels, remain unclear. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) is expressed on lymphatic vessel endothelium and is considered to be a specific marker of lymphatic vessels. However, it is unknown how LYVE-1 is involved in the growth and metastasis of cancer cells. We produced rat monoclonal antibodies (mAbs) recognizing the extracellular domain of mouse LYVE-1, and investigated the roles of LYVE-1 in tumor formation and metastasis...
July 30, 2018: Cancer Science
Yueh-Chien Lin, Chien-Chin Chen, Wei-Min Chen, Kuan-Ying Lu, Tang-Long Shen, Yeong-Chin Jou, Cheng-Huang Shen, Norihiko Ohbayashi, Yasunori Kanaho, Yuan-Li Huang, Hsinyu Lee
Lysophosphatidic acid (LPA) is a bioactive lipid growth factor which is present in high levels in serum and platelets. LPA binds to its specific G-protein-coupled receptors, including LPA1 to LPA6 , thereby regulating various physiological functions, including cancer growth, angiogenesis, and lymphangiogenesis. Our previous study showed that LPA promotes the expression of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C in prostate cancer (PCa) cells. Interestingly, LPA has been shown to regulate the expression of calreticulin (CRT), a multifunctional chaperone protein, but the roles of CRT in PCa progression remain unclear...
July 24, 2018: Biochimica et Biophysica Acta
Erin D Lucas, Jeffrey M Finlon, Matthew A Burchill, Mary K McCarthy, Thomas E Morrison, Tonya M Colpitts, Beth A Jirón Tamburini
Lymph node (LN) expansion during an immune response is a complex process that involves the relaxation of the fibroblastic network, germinal center formation, and lymphatic vessel growth. These processes require the stromal cell network of the LN to act deliberately to accommodate the influx of immune cells to the LN. The molecular drivers of these processes are not well understood. Therefore, we asked whether the immediate cytokines type 1 IFN produced during viral infection influence the lymphatic network of the LN in mice...
July 25, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiaolei Liu, Xiaowu Gu, Wanshu Ma, Michael Oxendine, Hyea Jin Gil, George E Davis, Ondine Cleaver, Guillermo Oliver
Although major progress in our understanding of the genes and mechanisms regulating lymphatic vasculature development has been made, we still do not know how lumen formation and maintenance occurs. Here we identify the Ras interacting protein Rasip1 as a key player in this process. We show that lymphatic endothelial cells-specific Rasip1 deficient embryos exhibit enlarged and blood-filled lymphatics at E14.5. These vessels have patent lumens with disorganized junctions. Later on, as those vessels become fragmented and lumens collapse, cell junctions become irregular...
July 24, 2018: Development
Sakthivel Chinnakkulam Kandhasamy, Thangadurai Ramasamy Raju, Ashok Kumar Sahoo, Gopalakrishnan Gunasekaran
Cystic lymphangioma of the parotid gland is an uncommon congenital lymphatic malformation. Its occurrence in patients of advanced age is infrequent. Patients usually present with painless soft swelling, often having experienced a long duration of symptoms. Lymphangioma among the salivary glands frequently involves the parotid gland. When evaluating cystic lesions of the parotid gland, cystic lymphangioma should be included in the differential diagnosis in addition to Warthin's tumor, branchial cyst, cystic pleomorphic adenoma, and cystic mucoepidermoid tumor...
May 18, 2018: Curēus
Zabeer Bhatti, Rameez Bhatti, Sharon Brangman, Kerry Whiting, Amit Dhamoon
Angiosarcoma is a cancer that is derived from endothelial cells that line blood vessels and lymphatic channels. Cutaneous angiosarcoma can appear anywhere on the skin and the clinical presentation is highly variable. Most cases appear on the scalp and face de novo. Our case describes a 91-year-old female with cutaneous scalp angiosarcoma. Our case serves to remind physicians that an abnormal skin finding in older adults should raise their index of suspicion for angiosarcoma and an early biopsy should be performed...
2018: Case Reports in Dermatological Medicine
Sinem Karaman, Veli-Matti Leppänen, Kari Alitalo
Vascular endothelial growth factors (VEGFs) are best known for their involvement in orchestrating the development and maintenance of the blood and lymphatic vascular systems. VEGFs are secreted by a variety of cells and they bind to their cognate tyrosine kinase VEGF receptors (VEGFRs) in endothelial cells to elicit various downstream effects. In recent years, there has been tremendous progress in elucidating different VEGF/VEGFR signaling functions in both the blood and lymphatic vascular systems. Here, and in the accompanying poster, we present key elements of the VEGF/VEGFR pathway and highlight the classical and newly discovered functions of VEGF signaling in blood and lymphatic vessel development and pathology...
July 20, 2018: Development
Paul M Kim, Jae-Jin Lee, Dongwon Choi, Hyungjin Eoh, Young-Kwon Hong
Mycobacterium tuberculosis (Mtb) has plagued humanity for tens of thousands of years, yet still remains a threat to human health. Its pathology is largely associated with pulmonary tuberculosis with symptoms including fever, hemoptysis, and chest pain. Mtb, however, also manifests in other extrapulmonary organs, such as the pleura, bones, gastrointestinal tract, central nervous system, and lymph nodes. Compared to the knowledge of pulmonary tuberculosis, extrapulmonary pathologies of Mtb are quite understudied...
July 2018: Tuberculosis
Yirui Zhu, Ling Li, Peter S Reinach, Yun Li, Chaoxiang Ge, Jia Qu, Wei Chen
Purpose: The purpose of this study was to determine whether corneal collagen crosslinking (CXL) inhibits hemangiogenesis and lymphangiogenesis during acute corneal inflammation in an in vivo rat model. Methods: Inflammatory corneal neovascularization was induced by suture placement into a rat cornea. At day 3 after suture, a CXL protocol using riboflavin and UVA was administered after mechanical epithelial debridement. Hemangiogenesis and lymphangiogenesis were analyzed morphometrically...
July 2, 2018: Investigative Ophthalmology & Visual Science
Morgan Preziosi, Hirohisa Okabe, Minakshi Poddar, Sucha Singh, Satdarshan P Monga
β-Catenin in hepatocytes, under the control of Wnts, regulates pericentral gene expression. It also contributes to liver regeneration (LR) after partial hepatectomy (PH) by regulating cyclin-D1 gene expression as shown in the β-catenin and Wnt coreceptors low-density lipoprotein receptor-related protein 5/6 conditional knockouts (KO). However, conditional deletion of Wntless (Wls), required for Wnt secretion, in hepatocytes, cholangiocytes, or macrophages lacked any impact on zonation, while Wls deletion in macrophages only marginally affected LR...
July 2018: Hepatology Communications
Yang Lee, Sanjukta Chakraborty, Cynthia J Meininger, Mariappan Muthuchamy
OBJECTIVE: Lymphatic vessel dysfunction and increased lymph leakage have been directly associated with several metabolic diseases. However, the underlying cellular mechanisms causing lymphatic dysfunction have not been determined. Aberrant insulin signaling affects the metabolic function of cells, and consequently impairs tissue function. We hypothesized that insulin resistance in lymphatic endothelial cells (LECs) decreases eNOS activity, disrupts barrier integrity increases permeability, and activates mitochondrial dysfunction and pro-inflammatory signaling pathways...
July 19, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Reiki Ogasawara, Daigo Hashimoto, Shunsuke Kimura, Eiko Hayase, Takahide Ara, Shuichiro Takahashi, Hiroyuki Ohigashi, Kosuke Yoshioka, Takahiro Tateno, Emi Yokoyama, Ko Ebata, Takeshi Kondo, Junichi Sugita, Masahiro Onozawa, Toshihiko Iwanaga, Takanori Teshima
The R-Spondin (R-Spo) family regulates WNT signaling and stimulates the proliferation and differentiation of intestinal stem cells (ISCs). R-Spo plays a critical role in maintaining intestinal homeostasis, but endogenous producers of R-Spo in the intestine remain to be investigated. We found that R-Spo3 was the major R-Spo family member produced in the intestine and it was predominantly produced by CD45- CD90+ CD31+ lymphatic endothelial cells (LECs) in the lamina propria of the intestinal mucosa. Transcriptome analysis demonstrated that LECs highly expressed R-Spo receptor, Lgr5, suggesting an autocrine stimulatory loop in LECs...
July 16, 2018: Scientific Reports
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