Kinetics of fibronectin release from fibroblasts in response to 12-O-tetradecanoylphorbol-13-acetate and retinoic acid
The authors have studied the effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and its in vivo and in vitro antagonist retinoic acid (RA) on the synthesis and release of a major extracellular glycoprotein, fibronectin (FN), in human lung fibroblasts (HLF). The studies reported here investigate the question of whether the increased amounts of FN released by TPA treatment are cell-surface derived or require de novo synthesis of FN. Untransformed HLF continuously released FN into the medium. Addition of TPA rapidly enhanced this release of FN into the culture medium, as shown with enzyme-linked immunosorbent assay. RA, given simultaneously with TPA, prevented the increased release and resulted in a normal FN accumulation in the medium. RA alone did not influence FN release. To study the effect of TPA or RA on synthesis rates of FN, HLF were labeled metabolically: FN synthesis rates with or without TPA, RA, or with TPA and RA were similar, as judged by assaying cell-layer-associated and medium (/sub 3/H)FN. They conclude that phorbol ester action and RA counteraction on the release of FN takes place on a cell-surface target; that FN which is released into the medium by TPA is derived from pre-existing FN; that RA specifically antagonizes TPA action. No protein synthesis is required to release FN, to mediate enhanced FN release by TPA, or to counteract the enhanced release by RA.
- Research Organization:
- Massachusetts Inst. of Tech., Cambridge
- OSTI ID:
- 6355228
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 5:7
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GLUCOPROTEINS
KINETICS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
RETINOIC ACID
BIOSYNTHESIS
CELL MEMBRANES
ENDOXAN
FIBROBLASTS
LUNGS
MAN
RADIOASSAY
TRITIUM COMPOUNDS
TUMOR PROMOTERS
ALKYLATING AGENTS
ANIMAL CELLS
ANIMALS
BODY
CARBOHYDRATES
CARBOXYLIC ACID ESTERS
CARCINOGENS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DRUGS
ESTERS
IMMUNOSUPPRESSIVE DRUGS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROMOTERS
PROTEINS
RESPIRATORY SYSTEM
SACCHARIDES
SOMATIC CELLS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques