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Modulation of cellular interactions between C3H/10T1/2 cells and their transformed counterparts by phosphodiesterase

J S Bertram

    Cancer Research
    |September 1, 1979
    PubMed

    Insights

    Non-transformed mouse fibroblasts inhibit malignant cell growth, a process influenced by cyclic nucleotides. The drug IBX effectively inhibits malignant transformation and promotes reversible growth arrest in transformed cells by increasing cyclic adenosine monophosphate (cAMP) levels.

    Area of Science:

    • Cell Biology
    • Biochemistry
    • Cancer Research

    Background:

    • Nontransformed C3H/10T1/2CL8 mouse fibroblasts (10T1/2) induce reversible growth inhibition in cocultured malignant fibroblasts.
    • This intercellular communication is modulated by serum concentration.

    Purpose of the Study:

    • To investigate the role of cyclic nucleotides in the growth inhibition of malignant cells by non-transformed fibroblasts.
    • To determine the effect of phosphodiesterase inhibitors on malignant transformation and cell growth.

    Main Methods:

    • Treatment of 3-methylcholanthrene-induced transformed mouse fibroblasts with phosphodiesterase inhibitors (theophylline, caffeine, 3-isobutyl-1-methylxanthine [IBX]).
    • Coculture experiments with non-transformed 10T1/2 cells and transformed cells.
    • Measurement of intracellular cyclic adenosine monophosphate (cAMP) levels.
    • Assessment of colony size, growth rate, plating efficiency, and saturation density.

    Main Results:

    • IBX demonstrated potent, dose-dependent inhibition of malignant transformation, with effects partially or completely reversible upon drug removal.
    • IBX inhibited transformed cell colony size in a dose-dependent manner, an effect potentiated by cAMP.
    • IBX treatment increased intracellular and extracellular cAMP levels in 10T1/2 cells.
    • The inhibitory effect of IBX on transformed cells required cell-cell contact and was specific to transformed cells, not affecting non-transformed cells.

    Conclusions:

    • Cyclic nucleotides, specifically cAMP, are implicated in the intercellular communication mediating growth inhibition of malignant cells by non-transformed fibroblasts.
    • IBX enhances the capacity of non-transformed 10T1/2 cells to induce reversible growth arrest in malignant cells, acting analogously to serum effects.

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