Diffusible Factors from Malignant Cells which Affect Epidermal Survival and Differentiation

Embryonic chick epidermis, if cultured for 4 days on a TH millipore filter overlying certain malignant dermal fibroblasts, shows abnormalities ranging from complete degeneration to hypertrophy and abnormal differentiation. The effect of the tumour cells is prevented if the thickness of the filter is doubled, to 50 μm., but not if a 25 μm.-thick membrane is coated with a thin collagen gel. When a semipermeable membrane is interposed between the cells and the epidermis, the latter does not degenerate, but keratinizes without showing the usual stages of differentiation. The malignant cells sometimes cause hypertrophy of the epidermis when cultured beneath the dermis of intact skin, but have no effect when grown on the peridermal surface of this tissue or of isolated epidermis. Freeze- or heat-killed dermal cells, whether normal or malignant, provide an unsuitable substratum for epidermal survival, possibly due to adsorption of intracellular constituents on to their surfaces. It is suggested that the malignant fibroblasts examined produce at least two substances having an effect on epidermis: one of small molecular size affecting differentiation, and a toxic macromolecule. A growth-promoting substance may also be produced by the cells of one subline. IMAGES: