Abstract
Three different human tumor lines in culture, a rhabdomyosarcoma, a bronchogenic carcinoma and a metastatic melanoma, release proteins (transforming growth factors, TGFs) into the medium that confer the transformed phenotype on untransformed fibroblasts. These proteins are acid and heat-stable; produce profound morphologic changes in rat and human fibroblasts; and enable normal anchorage-dependent cells to grow in agar. Removal of the transforming protein results in a reversion of cell phenotype. The major activity interacts with epidermal growth factor (EGF) cell membrane receptors. The peptides from these tumor cells are similar in their action to the sarcoma growth factor (SGF) released by murine sarcoma virus-transformed rodent cells. The most anchorage-independent tumor cells released the most TGFs. EGF-related TGFs were not detectable in fluids from cultures of cells with high numbers of free EGF membrane receptors (normal human fibroblasts and human carcinomas).
MeSH Terms
Adult
Aged
Animals
Binding, Competitive
Carcinoma, Bronchogenic/metabolism
Carcinoma, Squamous Cell/metabolism
Cell Division
Cell Transformation, Neoplastic
Cells, Cultured
DNA/biosynthesis
Epidermal Growth Factor/antagonists & inhibitors,metabolism
ErbB Receptors
Female
Fibroblasts
Growth Substances/metabolism
Humans
Lung Neoplasms/metabolism
Male
Melanoma/metabolism
Peptides/metabolism
Rats
Receptors, Cell Surface/metabolism
Rhabdomyosarcoma/metabolism
Chemicals
Growth Substances
Peptides
Receptors, Cell Surface
Epidermal Growth Factor
DNA
ErbB Receptors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Todaro G J
Fryling C
De Larco J E
References (20)
20 references, click to expand
-
In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors.
J Natl Cancer Inst. 1973 Nov;51(5):1417-23
PMID: 4357758
-
Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro.
Proc Natl Acad Sci U S A. 1975 Nov;72(11):4435-9
PMID: 172908
-
Nerve growth factor receptors on human melanoma cells in culture.
Proc Natl Acad Sci U S A. 1977 Feb;74(2):565-9
PMID: 265522
-
Test for malignant transformation of rat liver cells in culture: cytology, growth in soft agar, and production of plasminogen activator.
J Natl Cancer Inst. 1977 Dec;59(6):1651-8
PMID: 562943
-
Epithelioid and fibroblastic rat kidney cell clones: epidermal growth factor (EGF) receptors and the effect of mouse sarcoma virus transformation.
J Cell Physiol. 1978 Mar;94(3):335-42
PMID: 304450
-
The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin.
J Biol Chem. 1978 Apr 25;253(8):2769-76
PMID: 632300
-
Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431.
Proc Natl Acad Sci U S A. 1978 Jul;75(7):3317-21
PMID: 356052
-
Growth factors from murine sarcoma virus-transformed cells.
Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001-5
PMID: 211512
-
Growth factors produced by sarcoma virus-transformed cells.
Cancer Res. 1978 Nov;38(11 Pt 2):4147-54
PMID: 212188
-
Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor.
J Biol Chem. 1979 Jun 10;254(11):4884-91
PMID: 312292
-
Human melanoma cells have both nerve growth factor and nerve growth factor-specific receptors on their cell surfaces.
Proc Natl Acad Sci U S A. 1979 Mar;76(3):1288-92
PMID: 375235
-
Cycloheximide-dependent reversion of human cells transformed by MSV and chemical carcinogen.
Science. 1979 Aug 17;205(4407):691-3
PMID: 223242
-
Sarcoma growth factor from mouse sarcoma virus-transformed cells. Purification by binding and elution from epidermal growth factor receptor-rich cells.
J Biol Chem. 1980 Apr 25;255(8):3685-90
PMID: 6245088
-
Detection of epidermal growth factor-urogastrone and its receptor during fetal mouse development.
Proc Natl Acad Sci U S A. 1980 May;77(5):2782-5
PMID: 6248866
-
Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction.
Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494-8
PMID: 6251462
-
Murine sarcoma growth factors affect the growth and morphology of cultured mouse epithelial cells.
J Cell Physiol. 1980 Jul;104(1):41-6
PMID: 7440645
-
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75
PMID: 14907713
-
THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY.
Biochem J. 1963 Oct;89:114-23
PMID: 14097352
-
Persistent infection of a rat kidney cell line with Rauscher murine leukemia virus.
J Bacteriol. 1966 Oct;92(4):1133-40
PMID: 5926742
-
Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization.
J Biol Chem. 1972 Dec 10;247(23):7609-11
PMID: 4636326