Biomaterial Database

Glucocorticoids induce Kaposi's sarcoma cell proliferation through the regulation of transforming growth factor-beta. 1997

J Cai, and T Zheng, and M Lotz, and Y Zhang, and R Masood, and P Gill

Department of Internal Medicine, University of Southern California School of Medicine, Los Angeles, USA.

Glucocorticoid (GC) use is known to induce or enhance the growth of Kaposi's sarcoma (KS) in many clinical settings including human immunodeficiency virus infection, collagen vascular disease, lymphoproliferative disorders, and renal transplantation. Because GCs may induce immune suppression and thus tumor growth, we determined whether GCs had a direct effect on KS growth. We found that GCs directly induce the growth of KS cell lines. In examining the mechanism of action of GCs, we did not observe induction of known autocrine growth factors for KS including interleukin-1 (IL-1), IL-6, oncostatin-M, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF). We thus examined factor(s) that inhibit KS growth. Transforming growth factor-beta (TGF-beta) is produced by KS cells and has pleiotropic effects, including inhibiting the growth of hematopoietic and endothelial cells. We show that TGF-beta is produced by KS cells in both the latent and active forms, and that TGF-beta is an autocrine growth inhibitory factor. We then studied the effects of GCs on the regulation of TGF-beta and found that GCs do not inhibit TGF-beta transcription, but significantly inhibit TGF-beta activation. This effect is mediated through regulation of the TGF-beta activation pathway. TGF-beta is activated by plasmin which is positively regulated by plasminogen activator (PA) and PA receptor (PAR), and negatively regulated by plasminogen activator inhibitor (PAI). GCs downregulated PAR and upregulated PAI. Thus, glucocorticoids enhance KS cell growth through the regulation of TGF-beta activation.

UI	MeSH Term	Description	Entries
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D005434	Flow Cytometry	Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.	Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D005938	Glucocorticoids	A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.	Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012514	Sarcoma, Kaposi	A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Kaposi's sarcoma occurs spontaneously in Jewish and Italian males in Europe and the United States. An aggressive variant in young children is endemic in some areas of Africa. A third form occurs in about 0.04% of kidney transplant patients. There is also a high incidence in AIDS patients. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, pp2105-7) HHV-8 is the suspected cause.	Kaposi Sarcoma,Kaposi's Sarcoma,Multiple Idiopathic Pigmented Hemangiosarcoma,Kaposis Sarcoma,Sarcoma, Kaposi's
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016212	Transforming Growth Factor beta	A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.	Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk