Soluble fas antigen in serum of cancer patients

Abstract

Blood concentration of soluble Fas antigen is higher in patients with benign and malignant tumors in comparison with healthy subjects, which probably suggests its involvement into tumorigenesis. Key Words: tumors; apoptosis; soluble Fas antigenApoptosis, programmed cell death, is an important mechanism maintaining homeostasis in multicellular organisms. Disturbances in cell elimination underlie various pathological states such as malignant tumors, Alzheimer disease, multiple sclerosis, amyotrophic lateral sclerosis, thyroiditis, hepatitis, and autoimmune diseases.Fas/APO-1/CD95 is a type I transmembrane glycoprotein belonging to the TNF/NDF receptor family [5]. Fas is expressed in various tissues, in particular in the thymus, liver, heart, lungs; it is present on activated lymphocytes, natural killers, virus-infected and tumor cells.Similarly to tumor necrosis factor p55, Fas not only induces cell apoptosis upon interaction with specific ligand FasL or agonistic monoclonal antibodies (MCA) to Fas, but also activate transcription factor NtkB [14]. The mechanism triggering cell death via Fas is studied in detail. The interaction of Fas with FasL or agonistic MCA induces activation of caspase-8 or caspase-2 proteases via adapter proteins FADD/ MORT-1 or RIP and RAIDD, respectively [11,14] Molecular cloning studies and nucleotide-sequence analysis have demonstrated that apart from transmembrane Fas receptor, cells produce also soluble Fas (sFas), a product of alternative spicing of full-length Fas mRNA, which inhibits cytotoxicity induced by anti-Fas MCA in vitro [2,3]. Thus, enhanced production of sFas can underlie cell resistance to apoptosis.Elevated blood concentration of sFas was observed in some autoimmune disease: systemic lupus erythematosus [15] The aim of the present study was to determine serum concentration of sFas in patients with malignant tumors of various morphology and localization and to explore the relationship between sFas and these diseases. MATERIALS AND METHODSHybrid cells producing MCA to recombinant full-length Fas (Coultronics) were obtained according to a standard protocol [9]. Splenocytes from immunized BALB/c mice (3 intraperitoneal injections with a 2-week interval) were fused with mouse myeloma cells NSO/1

Modulation of apoptosis of mononuclear cells under conditions of oxidative stress

“…Among intracellular pathways, the mitochondrial pathway plays an important role, because of the presence of abundant proapoptotic factors (cytochrome C, Smac, AIF, endonuclease G) in mitochondria [8,12]. The release of these factors from the intermembrane space into cytosol activates procaspase-9, thus triggering apoptosis [1]. This process is impossible without opening of permeability transition pores between the outer and inner mitochondrial membranes and formation of channels in the outer membrane, which leads to a drop of transmembrane potential [12].…”

Leptin and apoptosis inhibitor soluble fas antigen in the serum of patients with osteosarcoma and neuroectodermal bone tumors

“…Serum concentration of sFas was measured by enzyme immunoassay [1], leptin by enzyme immunoassay with a DRG kit. Leptin and sFas levels in women were measured on days 21-24 of the cycle (cycle length 22-28 days).…”

“…Apoptosis is an extremely important mechanism maintaining homeostasis of multicellular organism, ensuring removal of damaged, aged, and "undesirable" cells without damaging cell microenvironment [7,10]. Impairment of apoptosis mechanisms is associated with pathological states, in particular, oncological diseases [1,11 ]. Many factors are involved in the mechanisms of apoptosis in normal and transformed cells.…”

“…Tumor growth, including tumor growth in the bones, results from imbalance between cell proliferation and apoptosis [ 1,11 ]. Apoptosis is an extremely important mechanism maintaining homeostasis of multicellular organism, ensuring removal of damaged, aged, and "undesirable" cells without damaging cell microenvironment [7,10].…”

“…A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow organs and tissues, including tumors, while FasL is expressed mainly in activated lymphocytes and natural killers. Soluble Fas (sFas), an alternative splicing product of full-length Fas mRNA, inhibiting Fas-dependent apoptosis, is intensely expressed in disease [ 1,9].…”