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Transforming growth factors in solid human malignant neoplasms.

K A Nickell, J Halper, H L Moses

    Cancer Research
    |May 1, 1983
    PubMed
    Summary

    Human tumors contain transforming growth factors (TGFs) that induce a reversible neoplastic phenotype in cells. These TGFs, including TGFa and TGFn, are polypeptides with varying molecular weights and are present in both benign and malignant tissues.

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    Area of Science:

    • Oncology
    • Molecular Biology
    • Biochemistry

    Background:

    • Transforming growth factors (TGFs) are polypeptide substances.
    • TGFs can induce a reversible neoplastic phenotype in cultured cells.
    • The presence and types of TGFs in human neoplasms are not fully characterized.

    Purpose of the Study:

    • To investigate the presence and characteristics of TGFs in surgically removed human benign and malignant neoplasms and nonneoplastic tissues.
    • To differentiate between various TGFs based on their activity and molecular weight.

    Main Methods:

    • Acid-ethanol extraction of human tissues.
    • Assay for colony-stimulating activity in soft agar using mouse AKR-2B and rat NRK cells.
    • Purification of active extracts using molecular sieve chromatography.
    • Characterization of TGF properties (heat, acid, trypsin, dithiothreitol stability).

    Main Results:

    • Extracts from various human tumors and nonneoplastic tissues stimulated soft agar growth of indicator cells.
    • TGF activity was heat and acid stable, destroyed by trypsin and dithiothreitol, indicating polypeptide nature with disulfide bonds.
    • At least three TGFs were identified: TGFa (AKR-2B selective), TGFn (NRK selective), with TGFn further divided into TGFns (small MW) and TGFnl (large MW).
    • TGFa and TGFnl were found in malignant and nonneoplastic tissues, while TGFns predominated in benign neoplasms.

    Conclusions:

    • Human tumors and nonneoplastic tissues contain multiple TGFs with distinct cellular specificities and molecular weights.
    • TGFa and TGFnl are associated with malignant and nonneoplastic tissues, whereas TGFns is more prevalent in benign neoplasms.
    • These TGFs represent distinct entities, with TGFnl activity potentiated by epidermal growth factor.

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