Search results for "Integrin"
showing 10 items of 286 documents
Modulation of proliferation and lymphokine secretion of murine CD4+ T cells and cloned Th1 cells by proteins of the extracellular matrix.
1997
In this study we investigated the co-stimulatory signaling capacity of diverse proteins of the extracellular matrix (ECM) for murine resting CD4+ T cells and Th1 clone cells, activated by immobilized anti-CD3 mAb. ECM proteins used in various concentrations had no effect on IL-2 production or proliferation of highly purified CD4+ T cell populations. When the preparation of CD4+ T cells contained contaminating accessory cells, IL-2 secretion and proliferation was enhanced in the presence of co-immobilized collagens or fibronectin. However, the level of proliferation attainable by added irradiated splenocytes was not reached. Using Th1 cell clone M4, enhanced production of IL-2 in the presenc…
β-Catenin Signaling Drives Differentiation and Proinflammatory Function of IRF8-Dependent Dendritic Cells
2014
Abstract β-Catenin signaling has recently been tied to the emergence of tolerogenic dendritic cells (DCs). In this article, we demonstrate a novel role for β-catenin in directing DC subset development through IFN regulatory factor 8 (IRF8) activation. We found that splenic DC precursors express β-catenin, and DCs from mice with CD11c-specific constitutive β-catenin activation upregulated IRF8 through targeting of the Irf8 promoter, leading to in vivo expansion of IRF8-dependent CD8α+, plasmacytoid, and CD103+CD11b− DCs. β-Catenin–stabilized CD8α+ DCs secreted elevated IL-12 upon in vitro microbial stimulation, and pharmacological β-catenin inhibition blocked this response in wild-type cells…
Migration of renal carcinoma cells is dependent on protein kinase Cδ via β1 integrin and focal adhesion kinase
2008
Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. In order to identify a connection between PKC isoforms and tumor progression in renal cell carcinoma (RCC), the influence of PKC isoforms on cell migration, adhesion and proliferation and possible influences of the activity of integrins and focal adhesion kinase (FAK) were analyzed in RCC cells. The experiments were performed in the RCC cell line CCF-RC1 after pre-incubation of the cells with the PKC inhibitors GF109203X, GO6976, RO31-8220 and rottlerin. Cell migration and adhesi…
CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphoc…
2009
AbstractCD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ versus CD38−CD49d− CLL cells, we showed overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also up-regulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38−CD49d− cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors…
Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release.
2011
In solid malignant tumors, lactate has been identified as a prognostic parameter for metastasis and overall survival of patients. To investigate the effects of lactate on tumor cell migration, Boyden chamber assays were applied. We could show here that lactate enhances tumor cell motility of head and neck carcinoma cell lines significantly in a dose-dependent manner. The changes in tumor cell migration could be attributed to L-lactate or a conversion of lactate to pyruvate, as only these two substances were able to increase migration. Addition of D-lactate or changes in osmolarity or intracellular pH did not alter the migratory potential of the cells investigated. Because lactate was shown …
Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic proge…
2001
Stromal cell-derived factor-1alpha (SDF-1alpha) is a potent chemoattractant for hematopoietic progenitor cells (HPC), suggesting that it could play an important role during their migration within or to the bone marrow (BM). The integrin VLA-4 mediates HPC adhesion to BM stroma by interacting with CS-1/fibronectin and VCAM-1. It is required during hematopoiesis and homing of HPC to the BM. As HPC migration in response to SDF-1alpha might require dynamic regulation of integrin function, we investigated if SDF-1alpha could modulate VLA-4 function on BM CD34(hi) cells.CD34(hi) BM cells and hematopoietic cell lines were tested for the effect of SDF-1alpha on VLA-4-dependent adhesion to CS-1/fibr…
Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion
2010
The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlat…
Differential inhibition of renal cancer cell invasion mediated by fibronectin, collagen IV and laminin.
2000
Invasion of tumor cells into the extracellular matrix is an essential step in the formation of metastases in renal cancer. Cell adhesion molecules such as beta(1)-integrins, which bind to the RGD sequence (arginine-glycine-asparagine) and CD44 are involved in this process. We examined the invasion of a renal carcinoma cell line (CCF-RC1) into the extracellular matrix compounds fibronectin, collagen IV and laminin and the effect of TGFbeta and IFNgamma on this process. The inhibitory effect of an antibody against the beta(1)-subunit of integrins (CD29), as well as a pentapeptide including the RGD sequence, was also evaluated. A micro-chemotaxis chamber, including a polycarbonate membrane wit…
Biotensegrity of the Extracellular Matrix: Physiology, Dynamic Mechanical Balance, and Implications in Oncology and Mechanotherapy
2014
Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is impli…
Genetic abrogation of the fibronectin-α5β1 integrin interaction in articular cartilage aggravates osteoarthritis in mice.
2018
The balance between synthesis and degradation of the cartilage extracellular matrix is severely altered in osteoarthritis, where degradation predominates. One reason for this imbalance is believed to be due to the ligation of the α5β1 integrin, the classic fibronectin (FN) receptor, with soluble FN fragments instead of insoluble FN fibrils, which induces matrix metalloproteinase (MMP) expression. Our objective was to determine whether the lack of α5β1-FN binding influences cartilage morphogenesis in vivo and whether non-ligated α5β1 protects or aggravates the course of osteoarthritis in mice. We engineered mice (Col2a-Cre;Fn1RGE/fl), whose chondrocytes express an α5β1 binding-deficient FN, …