Control of epidermal cell proliferation in vitro.

Epidermis from explants of keratome slices of domestic pig skin can be induced to migrate, proliferate, and stratify if at least two serum protein factors and a source of nucleosides are present. The factor which is necessary for cell movement or spreading is destroyed by heating the serum to 100 degrees C and is resistant to 80 degrees C heating. This factor has a molecular weight of 65,000 and is identical to the 'epibolin' found by Stenn. Proliferation is dependent on a serum factor which is destroyed by heating to 80 degrees C. However, cells which are denied this factor can make their own proliferation factor(s). Cell migration and cell proliferation usually occur together but they can be dissociated and are therefore independent phenomena. Increased cell proliferation can be achieved by some retinoids at the proper concentration but steroids, epidermal growth factor, a phorbol ester (TPA), and the use of injured skin as a keratome source failed to show in vitro hyperproliferation. Mitotic inhibition, however, can be induced by a variety of metabolic poisons (methotrexate, 5-fluorouracil, hydroxyurea), steroids, retinoids at high concentrations, and agents which increase adenosine 3',5'-monophosphate (cAMP).