Tumor growth stimulation in vitro by interferons.

Interferons (IFNs) are a family of polypeptides originally identified as antiviral substances. Subsequently, other properties of interferons were recognized, including inhibition of cell proliferation, and effects on the immune response and on expression of surface antigens. In this paper we present evidence that interferons, even the highly purified cloned IFNs, can stimulate clonogenic tumor growth in vitro. Of 225 human tumor (HT) samples tested with IFN in a clonogenic assay (HTCA), 30 (13.3%) showed growth stimulation (greater than 2 S.E. above control). The phenomenon was observed most frequently with acute myeloid leukemia (6/22 samples, 27.3%), and renal (2/10, 20%) and breast cancer (4/21, 19%), but significantly less frequent in melanomas (2/34, 5.9%). As an independent assessment of proliferation, tritiated thymidine uptake by tumor cells was measured autoradiographically in 21 patients with multiple myeloma. A significant increase of the thymidine labeling index was seen in 4 (19%) of the samples. Since this growth stimulatory effect was also observed with cell lines which lack any contaminating immunoreactive cells, there is strong evidence that interferons can directly stimulate the proliferation of clonogenic tumor cells in vitro. Growth stimulation by interferons occurred preferentially with lower dosages. It is important to be cognizant of potential clinical implications of tumor growth stimulation by interferons.