Comparison of transforming growth factor beta and a human tumour-derived suppressor factor. 1991

S S Somers, and J F Dye, and P J Guillou
Academic Surgical Unit, St. Mary's Hospital, London, England, UK.

Serum-free supernatants from the human melanoma cell line G361 contain a factor that can potently suppress the generation of tumouricidal lymphokine-activated killer (LAK) cells in response to interleukin-2. To characterise the suppressive factor of tumour origin we performed a number of physicochemical and functional comparisons with another immunosuppressive protein, transforming growth factor beta (TGF beta). The bioactivity of tumour-derived suppressor factor (TDSF), assayed by suppression of LAK cell generation, was unaffected by a reducing agent but lost when denatured with a chaotropic agent. In contrast, TGF beta was inactivated by reduction but not denaturation. TDSF lost bioactivity in conditions of pH less than 4, whereas TGF beta showed no loss of activity. The TDSF moiety has an estimated pI of 4.3 and a molecular mass of 69-87 kDa. This differs from published values of pI 9.5, and 25 kDa molecular mass for TGF beta. Anti-TGF beta antiserum reversed the effects of TGF beta but did not affect the suppression of LAK cell generation caused by TDSF. These findings provide compelling evidence that the TDSF moiety is not TGF beta, and may be a novel immunoregulatory cytokine.

UI MeSH Term Description Entries
D007526 Isoelectric Point The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. Isoelectric Points,Point, Isoelectric,Points, Isoelectric
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D013491 Suppressor Factors, Immunologic Proteins, protein complexes, or glycoproteins secreted by suppressor T-cells that inhibit either subsequent T-cells, B-cells, or other immunologic phenomena. Some of these factors have both histocompatibility (I-J) and antigen-specific domains which may be linked by disulfide bridges. They can be elicited by haptens or other antigens and may be mass-produced by hybridomas or monoclones in the laboratory. Immunologic Suppressor Factors,Suppressor T-Cell Factors,T-Cell Suppressive Factors,T-Suppressor Factors,Factors, Immunologic Suppressor,Factors, T Suppressor,Suppressor Factor (SF4),T Cell Suppressor Factors,Factors, Suppressor T-Cell,Factors, T-Cell Suppressive,Factors, T-Suppressor,Suppressive Factors, T-Cell,Suppressor Factors, T,Suppressor T Cell Factors,T Cell Suppressive Factors,T Suppressor Factors,T-Cell Factors, Suppressor
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
D015979 Killer Cells, Lymphokine-Activated Cytolytic lymphocytes with the unique capacity of killing natural killer (NK)-resistant fresh tumor cells. They are INTERLEUKIN-2-activated NK cells that have no MAJOR HISTOCOMPATIBILITY COMPLEX restriction or need for antigen stimulation. LAK cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients. LAK Cells,Lymphokine-Activated Killer Cells,Cell, LAK,Cell, Lymphokine-Activated Killer,Cells, LAK,Cells, Lymphokine-Activated Killer,Killer Cell, Lymphokine-Activated,Killer Cells, Lymphokine Activated,LAK Cell,Lymphokine Activated Killer Cells,Lymphokine-Activated Killer Cell
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

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