Introduction: Epidermolysis Bullosa (EB) is a rare genodermatosis characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma. There are three subtypes: EB Simplex, Junctional EB, and Dystrophic EB. Each type of EB has its own specific genetic defect. We report a case of a 13-year-old girl who presented with multiple tense blisters and eroded plaques since birth on the entire body. Case summary: This is a 13-year-old-girl who presented with solitary tense blister on her right thigh three days after birth, which gradually affected the scalp, trunk, and upper and lower extremities, particularly on the trauma prone areas. There was nail dystrophy and multiple brownish dental pits at three years of age. A 4 mm lesional skin punch biopsy showed subepidermal blisters containing fibrin, lymphocytes and few red blood cells. PAS showed basement membrane zone beneath the blister, compatible with EB. Immunofluorescence mapping showed decreased immunofluorescence (+1) on keratin 5/6, (+2) on keratin 14, and absence of immunofluorescence on alpha 6 / beta 4 integrins. Final diagnosis is EB Simplex. Conclusion Early detection is important in managing this case, to detect systemic involvement and provide palliative care. Genetic counseling is recommended for prospective parents who have a family history of any form of epidermolysis bullosa. The prognosis of Inherited EB is very variable and the mortality is usually due to complications of systemic involvement. A multidisciplinary approach in the supportive management of this case is necessary as there is still no cure for this condition.
Fluorescent Antibody Technique ; Integrins

Breast Neoplasms ; etiology ; Female ; Humans ; Integrins ; physiology

Recent years have seen an explosion of new knowledge defining the molecular events that are critical for development and activation of immune cells. Much of this new information has come from a careful molecular dissection of key signal transduction pathways that are initiated when immune cell receptors are engaged. In addition to the receptors themselves and critical effector molecules, these signaling pathways depend on adapters, proteins that have no intrinsic effector function but serve instead as scaffolds to nucleate multimolecular complexes. This review summarizes some of what has been learned about one such adapter protein, SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76), and how it regulates and integrates signals after engagement of immunoreceptors and integrins on various immune cell lineages.
Explosions ; Integrins ; Leukocytes ; Proteins ; Signal Transduction ; T-Lymphocytes

Integrins are a large family of heterodimeric cell adhesion molecules composed of α and β subunits. Through interaction with their specific ligands, integrins mediate cell-cell and cell-extracellular matrix interactions. Via outside-in signaling, integrins can recruit cytoplasmic proteins to their intracellular domains and then cluster into supramolecular structures and trigger downstream signaling. Integrin activation is associated with a global conformation rearrangement from bent to extended in ectodomains and the separation of α and β subunit cytoplasmic domains. During cell migration, integrins regulate the focal adhesion dynamics and transmit forces between the extracellular matrix and the cell cytoskeleton. In tumor microenvironment, integrins on multiple kinds of cells could be activated, which modulates cell migration into tumor and contributes to angiogenesis and tumor metastasis. Here, we review the mechanism of integrin activation, dynamics of focal adhesions during cell migration and tumor metastasis.
Cell Adhesion ; Cell Adhesion Molecules ; Focal Adhesions ; Integrins ; Signal Transduction

BACKGROUND: Osteopontin (OPN) is a cytokine associated with a cell-matrix via integrins. Fibroblast specific protein-1 (FSP-1), known as S100A4, has been implicated in cell migration by non-muscle myosin. We investigated whether the role of OPN and FSP-1/S100A4 expression in their contribution to the podocyte phenotype change to form podocyte bridge and cellular crescent. METHODS: Glomerular expression of OPN and FSP-1/S100A4 in renal biopsies of 16 patients with crescentic glomerulonephritis (CrGN) and 13 normal renal biopsies were studied by immunohistochemistry. RESULTS: The expression of OPN and FSP-1/S100A4 was increased in the podocytes of glomeruli, with and without crescents, in patients with CrGN. Neither OPN nor FSP-1/S100A4 was expressed in glomeruli from the normal controls (p<0.01). A significant positive correlation was found between the expression of OPN in glomerular tufts and cellular crescents, and the expression of OPN and FSP-1/S100A4 in glomerular tufts (p<0.05). CONCLUSIONS: The results suggest that OPN plays a role in early podocyte attachment to Bowman's capsule, and FSP-1/S100A4 potentiate podocyte contribution to cellular crescent formation by inducing cellular migration and growth.
Biopsy ; Bowman Capsule ; Cell Movement ; Fibroblasts ; Glomerulonephritis ; Humans ; Integrins ; Myosins ; Osteopontin ; Phenotype ; Podocytes

OBJECTIVES: In the metastatic process, interactions between circulating tumor cells (CTCs) and the extracellular matrix or surrounding cells are required. β1-integrin may mediate these interactions. The aim of this study was to investigate whether β1-integrin is associated with the detection of CTCs in colorectal cancer. METHODS: We enrolled 30 patients with colorectal cancer (experimental group) and 30 patients with benign diseases (control group). Blood samples were obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and β1-integrin mRNA levels were estimated by using reverse transcription-polymerase chain reaction, and the results were compared between the two groups. RESULTS: CEA mRNA was detected more frequently in colorectal cancer patients than in control patients (P=0.008). CEA mRNA was significantly reduced after surgery in the colorectal cancer patients (P=0.032). β1-integrin mRNA was detected more in colorectal cancer patients than in the patients with benign diseases (P<0.001). In colorectal cancer patients, expression of β1-integrin mRNA was detected more for advanced-stage cancer than for early-stage cancer (P=0.033) and was significantly decreased after surgery (P<0.001). In addition, expression of β1-integrin mRNA was significantly associated with that of CEA mRNA in colorectal cancer patients (P=0.001). CONCLUSION: In conclusion, β1-integrin is a potential prognostic factor following surgical resection in colorectal cancer patients. β1-integrin may be a candidate for use as a marker for early detection of micrometastatic tumor cells and for monitoring the therapeutic response in colorectal cancer patients.
Carcinoembryonic Antigen ; Case-Control Studies* ; Colorectal Neoplasms* ; Extracellular Matrix ; Humans ; Integrins ; Neoplastic Cells, Circulating ; RNA, Messenger

OBJECTIVETo study the integrin beta3 mRNA changes after orthodontic treatment on normal teeth and periodontitis teeth in rats.

METHODS96 adult SD rats of 10 weeks old were randomly divided into normal tooth move-ment group and periodontitis tooth movement group. The rats in the two groups were sacrificed after 0 d, 12 h, 1 d, 3 d, 5 d and 7 d of tooth movement. The alveolar specimens were prepared. The integrin beta3 mRNA were detected using in situ hybridization in the specimens. The OD index of positively stained osteoclasts for integrin beta3 mRNA after orthodontic tooth movement in the two groups were measured and compared.

RESULTSThere were weak positive signals on the cytoplasm of osteoclasts in periodontum in both groups after 12 hours and 3 days force activation. No positive signals were detected in the rest samples. There was no difference in the OD of positive stained osteoclasts between normal and periodontitis groups. Strong expressions were present on cells with one or two nuclei in the alveolar marrow.

CONCLUSIONIt is suggested that integrin beta3 mRNA is related with osteoclasts maturation and migration in orthodontic tooth movement.

Low shear stress is a component of the tumor microenvironment in vivo and plays a key role in regulating cancer cell migration and invasion. The integrin, as a mechano-sensors mediating and integrating mechanical and chemical signals, induce the adhesion between cells and extracellular matrix (ECM). The purpose of this study is to investigate the effect of low shear stress (1.4 dyn/cm2)on the migration of HepG2 cells and the expression of integrin. Scratch wound migration assay was performed to examine the effect of low shear stress on the migration of HepG2 cells at 0 h, 1 h, 2 h and 4 h, respectively. F-actin staining was used to detect the expression of F-actin in HepG2 cells treated with low shear stress at 2 h and 4 h. Western blot analysis was carried out to determine the effect of low shear stress on the expression of integrin at different durations. The results showed that the migrated distance of HepG2 cells and the expression of F-actin increased significantly compared with the controls. The integrin alpha subunits showed a different time-dependent expression, suggesting that various subunits of integrin exhibit different effects in low shear stress regulating cancer cells migration.
Actins ; physiology ; Cell Movement ; Extracellular Matrix ; physiology ; Hep G2 Cells ; Humans ; Integrins ; physiology ; Stress, Mechanical

Tumor cells exhibit two main different migration strategies when invading in 3D environment, i. e. mesenchymal migration and amoeboid migration. This review summarizes the internal reasons and characteristics on various modes of migration adaptation to the microenvironment, and the molecular mechanisms in particular environment where they are mutually interchangeable. A study of the mechanisms that may possibly trigger mesenchymal-amoeboid transition/amoeboid-mesenchymal transition help us to understand the change and the plasticity in the migration strategies of tumor cells. These are important for the development of a cancer treatment, which would efficiently suppress tumor cell invasiveness.
Cell Movement ; physiology ; Extracellular Matrix ; pathology ; Humans ; Integrins ; physiology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; physiopathology

Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.
Cytoskeletal Proteins ; Endothelial Cells ; Extracellular Traps ; Integrins ; Intercellular Adhesion Molecule-1 ; Lipopolysaccharides/pharmacology* ; Macrophages ; Neutrophils