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Gap junctions tumor antigen

Yvona Ward, Ross Lake, Farhoud Faraji, Jamie Sperger, Philip Martin, Cameron Gilliard, Kimberly P Ku, Tamara Rodems, David Niles, Heather Tillman, JuanJuan Yin, Kent Hunter, Adam G Sowalsky, Joshua Lang, Kathleen Kelly
Tumor cells initiate platelet activation leading to the secretion of bioactive molecules, which promote metastasis. Platelet receptors on tumors have not been well-characterized, resulting in a critical gap in knowledge concerning platelet-promoted metastasis. We identify a direct interaction between platelets and tumor CD97 that stimulates rapid bidirectional signaling. CD97, an adhesion G protein-coupled receptor (GPCR), is an overexpressed tumor antigen in several cancer types. Purified CD97 extracellular domain or tumor cell-associated CD97 stimulated platelet activation...
April 17, 2018: Cell Reports
Seyed-Alireza Esmaeili, Foroogh Nejatollahi, Amirhossein Sahebkar
BACKGROUND: Six-Transmembrane epithelial antigen of the prostate-1 (STEAP-1) is present at the intercellular junctions of the secretory epithelium of prostate and is overexpressed in all steps of prostate cancer. STEAP-1 acts as a transporter protein or a putative channel between cancer cells while it has limited expression in normal human tissues. This protein has been suggested as an attractive target for prostate cancer immunotherapy. OBJECTIVE: This study aimed at the development of a specific single chain fragment variable (scFv) antibody against STEAP-1 epitope and testing the inhibitory effect of the selected scFv antibody in blocking gap junctions between tumor cells...
December 7, 2017: Anti-cancer Agents in Medicinal Chemistry
María Alejandra Gleisner, Mariela Navarrete, Francisca Hofmann, Flavio Salazar-Onfray, Andrés Tittarelli
Gap junctions (GJs)-mediated intercellular communications (GJICs) are connexin (Cx)-formed plasma membrane channels that allow for the passage of small molecules between adjacent cells, and are involved in several physiopathological processes, including immune responses against cancer. In general, tumor cells are poorly coupled through GJs, mainly due to low Cx expression or reduced channel activity, suggesting that Cxs may have tumor suppressor roles. However, more recent data indicate that Cxs and/or GJICs may also in some cases promote tumor progression...
2017: Frontiers in Immunology
Joana Gonçalves, Ricardo A Leitão, Alejandro Higuera-Matas, María Amparo Assis, Santiago M Coria, Carlos Fontes-Ribeiro, Emilio Ambrosio, Ana Paula Silva
Methamphetamine (METH) is a highly addictive psychostimulant drug that can lead to neurological and psychiatric abnormalities. Several studies have explored the central impact of METH use, but the mechanism(s) underlying blood-brain barrier (BBB) dysfunction and associated neuroinflammatory processes after chronic METH consumption are still unclear. Important findings in the field are mainly based on in vitro approaches and animal studies using an acute METH paradigm, and not much is known about the neurovascular alterations under a chronic drug use...
May 2017: Brain, Behavior, and Immunity
Mulu Geletu, Stephanie Guy, Samantha Greer, Leda Raptis
Gap junctions are channels that connect the cytoplasm of adjacent cells. Oncogenes such as the middle Tumor antigen of polyoma virus (mT) are known to suppress gap junctional, intercellular communication (GJIC). mT associates with and is tyrosine-phosphorylated by cSrc family members. Specific mT phosphotyrosines provide docking sites for the phosphotyrosine binding domain of Shc (mT-tyr250) or the SH2 domain of the regulatory subunit of the phosphatidylinositol-3 kinase (PI3k, mT-tyr315). Binding results in the activation of their downstream signaling cascades, Ras/Raf/Erk and PI3 kinase/Akt, respectively, both of which are needed for full neoplastic transformation...
August 15, 2015: Experimental Cell Research
Håkon Reikvam, Anita Ryningen, Lars Rune Sæterdal, Ina Nepstad, Brynjar Foss, Øystein Bruserud
Bone marrow stromal cells support both normal and malignant hematopoiesis. Τhis support is mediated through the local cytokine network and by direct cell‑cell interactions mediated via adhesion molecules and the formation of gap junctions by connexins. Previous studies on connexins in human acute myeloid leukemia (AML) have mainly focused on the investigation of leukemia cell lines. In the present study, we therefore investigated the expression of various connexins at the protein (i.e., cell surface expression) and mRNA level in primary human AML cells...
March 2015: International Journal of Molecular Medicine
Pu Zhang, Changliang Fu, Huiyuan Bai, Erqun Song, Yang Song
Loss of endothelial adherens junctions is involved in tumor metastasis. Here, we demonstrate that, in the metastatic Lu1205 melanoma cells, expression of the CD44 variant CD44v8-v10 induced junction disassembly and vascular endothelial (VE)-cadherin phosphorylation at Y658 and Y731. Short interfering RNA (siRNA)-mediated CD44 knockdown or sialic acid cleavage reversed these effects. Moreover, microspheres coated with recombinant CD44v8-v10 promoted endothelial junction disruption. Overexpression of CD44v8-v10 but not of standard CD44 (CD44s) promoted gap formation in the non-metastatic WM35 melanoma cells, whereas CD44 knockdown or neuraminidase treatment dramatically diminished melanoma transendothelial migration...
December 20, 2014: FEBS Letters
Jia-Huan Li, Gang-Jun Du, Wei-Jie Liu, Ying-Hui Liu, Bei Zhao, Hong Li
OBJECTIVE: To observe the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer, and study its anti-tumor mechanism. METHOD: In vitro, MTT assay and scratch assay were adopted to detect the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer cells. The cell autophagy was detected by the acridine orange staining. The gap-junction intercellular communication (GJIC) was investigated by the fluorescent yellow transfer...
March 2014: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Valerie Amsellem, Nicola H Dryden, Roberta Martinelli, Felicity Gavins, Lourdes Osuna Almagro, Graeme M Birdsey, Dorian O Haskard, Justin C Mason, Patric Turowski, Anna M Randi
BACKGROUND: Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis...
March 4, 2014: Cell Communication and Signaling: CCS
Ann L B Seynhaeve, Joost A P Rens, Debby Schipper, Alexander M M Eggermont, Timo L M Ten Hagen
BACKGROUND AND PURPOSE: We demonstrated previously that the administration of tumor necrosis factor alpha (TNF-α) for the treatment of solid tumors enhanced the response to chemotherapy by augmenting intratumoral drug accumulation. TNF-α changes the integrity of the endothelial cell monolayer in combination with interferon gamma (IFN-γ), which is further enhanced by the addition of peripheral blood mononuclear cells (PBMCs). The improved effect of PBMCs was mostly induced by the endogenous production of interleukin-1beta (IL-1ß) after TNF-α stimulation...
March 2014: Surgery
Xin Song, Hui-Xin Chen, Xiao-Yan Wang, Xi-Yun Deng, Yin-Xue Xi, Qing He, Tie-Li Peng, Jie Chen, Wei Chen, Benjamin Chun-Yu Wong, Min-Hu Chen
Helicobacter pylori encoded CagA is presently the only known virulence factor that is injected into gastric epithelial cells where it destroys apical junctional complexes and induces dedifferentiation of gastric epithelial cells, leading to H. pylori-related gastric carcinogensis. However, little is known about the molecular mechanisms by which CagA mediates these changes. Caudal-related homeobox 2 (Cdx2) is an intestine-specific transcription factor highly expressed in multistage tissues of dysplasia and cancer...
November 2013: Cellular Immunology
Jonathan M Williams, Carrie A Duckworth, Alastair J M Watson, Mark R Frey, Jennifer C Miguel, Michael D Burkitt, Robert Sutton, Kevin R Hughes, Lindsay J Hall, Jorge H Caamaño, Barry J Campbell, D Mark Pritchard
The gut barrier, composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, prevents the entrance of harmful microorganisms, antigens and toxins from the gut lumen into the blood. Small intestinal homeostasis is normally maintained by the rate of shedding of senescent enterocytes from the villus tip exactly matching the rate of generation of new cells in the crypt. However, in various localized and systemic inflammatory conditions, intestinal homeostasis can be disturbed as a result of increased IEC shedding...
November 2013: Disease Models & Mechanisms
Houssem Benlalam, Thibault Carré, Abdelali Jalil, Zaeem Noman, Bernard Caillou, Philippe Vielh, Andrés Tittarelli, Caroline Robert, Salem Chouaib
UNLABELLED: Gap junctions (GJs) enable intercellular communication between adjacent cells through channels of connexins. Using a three-dimensional construct, we previously showed that endothelial and tumor cells formed GJs, allowing melanoma-specific T lymphocytes to recognize and kill melanoma-derived endothelial cells. We demonstrate here on histological sections of melanoma biopsies that GJ formation occurs in vivo between tumor and endothelial cells and between T lymphocytes and target cells...
October 2013: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Ivett Teleki, Tibor Krenacs, Marcell A Szasz, Janina Kulka, Barna Wichmann, Cornelia Leo, Barbel Papassotiropoulos, Cosima Riemenschnitter, Holger Moch, Zsuzsanna Varga
BACKGROUND: Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST) are still missing. Deregulation of gap junction channel forming connexins (Cx) has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems...
February 2, 2013: BMC Cancer
Hyang Jee, Su-Hyung Lee, Jun-Won Park, Bo-Ram Lee, Ki-Taek Nam, Dae-Yong Kim
Gap junctions and their structural proteins, connexins (Cxs), have been implicated in carcinogenesis. To explore the involvement of Cx32 in gastric carcinogenesis, immunochemical analysis of Cx32 and proliferation marker Ki67 using tissue-microarrayed human gastric cancer and normal tissues was performed. In addition, after Cx32 overexpression in the human gastric cancer cell line AGS, cell proliferation, cell cycle analyses, and p21(Cip1) and p27(Kip1) expression levels were examined by bromodeoxyuridine assay, flow cytometry, real-time RT-PCR, and western blotting...
January 2013: BMB Reports
Shyam A Patel, Shakti H Ramkissoon, Margarette Bryan, Lillian F Pliner, Gabriela Dontu, Prem S Patel, Sohrab Amiri, Sharon R Pine, Pranela Rameshwar
The bone marrow (BM) is a major organ of breast cancer (BC) dormancy and a common source of BC resurgence. Gap junctional intercellular communication (GJIC) between BC cells (BCCs) and BM stroma facilitates dormancy. This study reports on a hierarchy of BCCs with the most immature subset (Oct4(hi)/CD44(hi/med)/CD24(-/+)) demonstrating chemoresistance, dormancy, and stem cell properties: self-renewal, serial passaging ability, cycling quiescence, long doubling time, asymmetric division, high metastatic and invasive capability...
2012: Scientific Reports
Pilar Alcaide, Roberta Martinelli, Gail Newton, Marcie R Williams, Alejandro Adam, Peter A Vincent, Francis W Luscinskas
Leukocyte transendothelial migration (TEM) is regulated by several signaling pathways including Src family kinases (SFK) and the small RhoGTPases. Previous studies have shown that vascular endothelial-cadherin (VE-cad) forms a complex with β-,γ-, and p120-catenins and this complex disassociates to form a transient gap during leukocyte TEM. Additionally, p120-catenin (p120-1A) overexpression in human umbilical vein endothelial cells (HUVEC) stabilizes VE-cad surface expression, prevents tyrosine phosphorylation of VE-cad, and inhibits leukocyte TEM...
August 15, 2012: American Journal of Physiology. Cell Physiology
Ricarda Wuestefeld, Jingchen Chen, Karl Meller, Beate Brand-Saberi, Carsten Theiss
The purpose of the present study was to investigate the effects of vascular endothelial growth factor (VEGF) on gap junctional intercellular communication (GJIC), cell proliferation, and cell dynamics in primary astrocytes. VEGF is known as a dimeric polypeptide that potentially binds to two receptors, VEGFR-1 and VEGFR-2, however many effects are mediated by VEGFR-2, for example, actin polymerization, forced cell migration, angiogenesis, and cell proliferation. Recently it has been shown that in case of hypoxia, ischemia or injury VEGF is upregulated to stimulate angiogenesis and cell proliferation...
May 2012: Glia
Bernard Caillou, Monique Talbot, Urbain Weyemi, Catherine Pioche-Durieu, Abir Al Ghuzlan, Jean Michel Bidart, Salem Chouaib, Martin Schlumberger, Corinne Dupuy
BACKGROUND: A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. METHODOLOGY/PRINCIPAL FINDINGS: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used...
2011: PloS One
Marko Boban, Neven Ljubicic, Marko Nikolic, Davor Tomas, Mario Zovak, Miroslav Bekavac-Beslin, Borislav Belev, Jasna Radic, Milan Milosevic
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors with variable malignant potential. Connexin-43 (Cx43) is the commonest gap-junction protein and has been frequently investigated in oncology. Our aim was to establish the immunohistochemical expression of Cx43 in relation to GIST location, size, Ki67 index, tumor grade and follow-up.? MATERIALS AND METHODS: The study included postoperative samples of 46 patients treated for GIST in the 1999-2010 time frame...
April 2011: International Journal of Biological Markers
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