PMID- 24569142 OWN - NLM STAT- MEDLINE DCOM- 20140605 LR - 20210102 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 323 IP - 1 DP - 2014 Apr 15 TI - Dendritic cells: In vitro culture in two- and three-dimensional collagen systems and expression of collagen receptors in tumors and atherosclerotic microenvironments. PG - 7-27 LID - S0014-4827(14)00051-2 [pii] LID - 10.1016/j.yexcr.2014.01.031 [doi] AB - Dendritic cells (DCs) are immune cells found in the peripheral tissues where they sample the organism for infections or malignancies. There they take up antigens and migrate towards immunological organs to contact and activate T lymphocytes that specifically recognize the antigen presented by these antigen presenting cells. In the steady state there are several types of resident DCs present in various different organs. For example, in the mouse, splenic DC populations characterized by the co-expression of CD11c and CD8 surface markers are specialized in cross-presentation to CD8 T cells, while CD11c/SIRP-1alpha DCs seem to be dedicated to activating CD4 T cells. On the other hand, DCs have also been associated with the development of various diseases such as cancer, atherosclerosis, or inflammatory conditions. In such disease, DCs can participate by inducing angiogenesis or immunosuppression (tumors), promoting autoimmune responses, or exacerbating inflammation (atherosclerosis). This change in DC biology can be prompted by signals in the microenvironment. We have previously shown that the interaction of DCs with various extracellular matrix components modifies the immune properties and angiogenic potential of these cells. Building on those studies, herewith we analyzed the angiogenic profile of murine myeloid DCs upon interaction with 2D and 3D type-I collagen environments. As determined by PCR array technology and quantitative PCR analysis we observed that interaction with these collagen environments induced the expression of particular angiogenic molecules. In addition, DCs cultured on collagen environments specifically upregulated the expression of CXCL-1 and -2 chemokines. We were also able to establish DC cultures on type-IV collagen environments, a collagen type expressed in pathological conditions such as atherosclerosis. When we examined DC populations in atherosclerotic veins of Apolipoprotein E deficient mice we observed that they expressed adhesion molecules capable of interacting with collagen. Finally, to further investigate the interaction of DCs with collagen in other pathological conditions, we determined that both murine ovarian and breast cancer cells express several collagen molecules that can contribute to shape their particular tumor microenvironment. Consistently, tumor-associated DCs were shown to express adhesion molecules capable of interacting with collagen molecules as determined by flow cytometry analysis. Of particular relevance, tumor-associated DCs expressed high levels of CD305/LAIR-1, an immunosuppressive receptor. This suggests that signaling through this molecule upon interaction with collagen produced by tumor cells might help define the poorly immunogenic status of these cells in the tumor microenvironment. Overall, these studies demonstrate that through interaction with collagen proteins, DCs can be capable of modifying the microenvironments of inflammatory disease such as cancer or atherosclerosis. CI - Copyright (c) 2014. Published by Elsevier Inc. FAU - Sprague, Leslee AU - Sprague L AD - Biomedical Engineering Program, Russ College of Engineering and Technology, Ohio University, USA. FAU - Muccioli, Maria AU - Muccioli M AD - Molecular and Cellular Biology Program, Ohio University, USA. FAU - Pate, Michelle AU - Pate M AD - Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, USA. FAU - Singh, Manindra AU - Singh M AD - Molecular and Cellular Biology Program, Ohio University, USA. FAU - Xiong, Chengkai AU - Xiong C AD - Biomedical Engineering Program, Russ College of Engineering and Technology, Ohio University, USA. FAU - Ostermann, Alexander AU - Ostermann A AD - Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, USA. FAU - Niese, Brandon AU - Niese B AD - Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, USA. FAU - Li, Yihan AU - Li Y AD - Molecular and Cellular Biology Program, Ohio University, USA. FAU - Li, Yandi AU - Li Y AD - Molecular and Cellular Biology Program, Ohio University, USA. FAU - Courreges, Maria Cecilia AU - Courreges MC AD - Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, USA. FAU - Benencia, Fabian AU - Benencia F AD - Biomedical Engineering Program, Russ College of Engineering and Technology, Ohio University, USA; Molecular and Cellular Biology Program, Ohio University, USA; Diabetes Institute, Ohio University, USA; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, USA. Electronic address: benencia@ohio.edu. LA - eng GR - R15CA137499-01/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140222 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Apolipoproteins E) RN - 0 (CD11c Antigen) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CXCL1) RN - 0 (Chemokine CXCL2) RN - 0 (Cxcl1 protein, mouse) RN - 0 (Cxcl2 protein, mouse) RN - 0 (Integrin alpha1beta1) RN - 0 (Integrin alpha2beta1) RN - 0 (Integrin alpha3beta1) RN - 0 (Msr1 protein, mouse) RN - 0 (Receptors, Collagen) RN - 0 (Receptors, Immunologic) RN - 0 (Scavenger Receptors, Class A) RN - 0 (leukocyte-associated immunoglobulin-like receptor 1) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Apolipoproteins E/genetics MH - Atherosclerosis/immunology/*metabolism MH - Breast Neoplasms/immunology/*metabolism MH - CD11c Antigen/metabolism MH - Cell Adhesion Molecules/metabolism MH - Cell Culture Techniques MH - Cell Line, Tumor MH - Cell Proliferation MH - Chemokine CXCL1/biosynthesis MH - Chemokine CXCL2/biosynthesis MH - Chemotaxis MH - Collagen/metabolism MH - Dendritic Cells/*metabolism MH - Female MH - Integrin alpha1beta1/biosynthesis/metabolism MH - Integrin alpha2beta1/biosynthesis/metabolism MH - Integrin alpha3beta1/biosynthesis/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neoplasms, Experimental/immunology/metabolism MH - Neovascularization, Physiologic MH - Ovarian Neoplasms/immunology/*metabolism MH - Receptors, Collagen/biosynthesis/*metabolism MH - Receptors, Immunologic/biosynthesis/metabolism MH - Scavenger Receptors, Class A/biosynthesis/metabolism MH - Tumor Microenvironment MH - Up-Regulation OTO - NOTNLM OT - Angiogenesis OT - Antigen presentation OT - Atherosclerosis OT - Breast cancer OT - Collagen OT - Dendritic cells OT - Ovarian cancer EDAT- 2014/02/27 06:00 MHDA- 2014/06/06 06:00 CRDT- 2014/02/27 06:00 PHST- 2012/07/03 00:00 [received] PHST- 2014/01/25 00:00 [revised] PHST- 2014/01/28 00:00 [accepted] PHST- 2014/02/27 06:00 [entrez] PHST- 2014/02/27 06:00 [pubmed] PHST- 2014/06/06 06:00 [medline] AID - S0014-4827(14)00051-2 [pii] AID - 10.1016/j.yexcr.2014.01.031 [doi] PST - ppublish SO - Exp Cell Res. 2014 Apr 15;323(1):7-27. doi: 10.1016/j.yexcr.2014.01.031. Epub 2014 Feb 22.