PMID- 22551928 OWN - NLM STAT- MEDLINE DCOM- 20130517 LR - 20211021 IS - 1878-3279 (Electronic) IS - 0171-2985 (Print) IS - 0171-2985 (Linking) VI - 218 IP - 1 DP - 2013 Jan TI - Adhesion to substrates induces dendritic cell endothelization and decreases immunological response. PG - 64-75 LID - S0171-2985(12)00039-3 [pii] LID - 10.1016/j.imbio.2012.02.003 [doi] AB - Dendritic cells (DCs) are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. DCs have been shown to possess a high plasticity showing different phenotypes in response to their microenvironment. For example, tumor-associated DCs can acquire an angiogenic phenotype thus promoting tumor growth. Further, DCs cultured in vitro under different conditions are able to upregulate the expression of endothelial markers and to express angiogenic factors. Indeed, it has been shown that soluble factors such as VEGF of PGE-2, that are present in the microenvironment of several tumors, affect the biology of these cells. We hypothesize that in addition to soluble factors the adhesion to different substrates will also define the phenotype and function of DCs. Herewith we demonstrate that murine myeloid(m) DCs upregulate endothelial markers such as VE-Cadherin, and to a lesser extent TIE-2, and decrease their immune capabilities when cultured on solid surfaces as compared with the same cells cultured on ultra-low binding (ULB) surfaces. On the other hand, the expression of angiogenic molecules at the level of RNA was not different among these cultures. In order to further investigate this phenomenon we used the murine ID8 model of ovarian cancer which can generate solid tumors when cancer cells are injected subcutaneously or a malignant ascites when they are injected intraperitoneally. This model gave us the unique opportunity to investigate DCs in suspension or attached to solid surfaces under the influence of the same tumor cells. We were able to determine that DCs present in solid tumors showed higher levels of expression of endothelial markers and angiogenic molecules but were not able to respond to inflammatory stimuli at the same extent as DCs recovered from ascites. Moreover, mDCs cultured on ULB surfaces in the presence of tumor factors do not expressed endothelial markers. Taking into account all these data we consider that tumor factors might be responsible for inducing angiogenic properties in DCs, but that in some settings the expression of endothelial markers such as VE-Cadherin and TIE-2 might be a function of attachment to solid surfaces and independent of the angiogenic properties of these cells. CI - Copyright (c) 2012 Elsevier GmbH. All rights reserved. FAU - Osterbur, Jacob AU - Osterbur J AD - Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA. FAU - Sprague, Leslee AU - Sprague L FAU - Muccioli, Maria AU - Muccioli M FAU - Pate, Michelle AU - Pate M FAU - Mansfield, Kristen AU - Mansfield K FAU - McGinty, John AU - McGinty J FAU - Li, Yihan AU - Li Y FAU - Li, Yandi AU - Li Y FAU - Shirure, Venktesh AU - Shirure V FAU - Courreges, Maria Cecilia AU - Courreges MC FAU - Benencia, Fabian AU - Benencia F LA - eng GR - R15 CA137499/CA/NCI NIH HHS/United States GR - R15 CA137499-01/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120227 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Antigens, CD) RN - 0 (Cadherins) RN - 0 (Interleukin-6) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (cadherin 5) RN - 0 (vascular endothelial growth factor A, mouse) RN - EC 2.7.10.1 (Receptor, TIE-2) SB - IM MH - Animals MH - Antigens, CD/genetics/metabolism MH - Cadherins/genetics/metabolism MH - Cell Adhesion/immunology MH - Cell Differentiation MH - Cell Line, Tumor MH - Dendritic Cells/*immunology MH - Endothelium/immunology/*metabolism MH - Female MH - Humans MH - Interleukin-6/genetics/metabolism MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Ovarian Neoplasms/*immunology MH - Receptor, TIE-2/genetics/metabolism MH - Tumor Microenvironment MH - Up-Regulation MH - Vascular Endothelial Growth Factor A/genetics/metabolism PMC - PMC3413747 MID - NIHMS360485 EDAT- 2012/05/04 06:00 MHDA- 2013/05/18 06:00 PMCR- 2014/01/01 CRDT- 2012/05/04 06:00 PHST- 2011/07/11 00:00 [received] PHST- 2012/02/01 00:00 [revised] PHST- 2012/02/04 00:00 [accepted] PHST- 2012/05/04 06:00 [entrez] PHST- 2012/05/04 06:00 [pubmed] PHST- 2013/05/18 06:00 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - S0171-2985(12)00039-3 [pii] AID - 10.1016/j.imbio.2012.02.003 [doi] PST - ppublish SO - Immunobiology. 2013 Jan;218(1):64-75. doi: 10.1016/j.imbio.2012.02.003. Epub 2012 Feb 27.