Stimulation of clonal tumor cell growth in vitro by inhibiting the serum polyamine oxidase activity.

Abstract

Several tumors are characterized by elevated levels of polyamines involved in vital cell proliferation processes. Polyamine oxidases (PAO), present in ruminant and particularily in fetal calf serum (FCS), degrade polyamines to polyaminoaldehydes and other products that inhibit cell proliferation. Since most in vitro assays for cloning tumor stem cells use FCS as an essential supplement of the nutrient media, we examined the effects of specifically inhibiting the PAO activity on the clonal growth of leukemic cells and the following normal lymphocytes: the W 25 rat chloroleukemia, the M1 mouse myeloblastic and the L 1210 rat lymphoblastic leukemia, a primary human acute myeloblastic leukemia (AML) and acute lymphocytic leukemia (ALL) as well as normal human PHA-stimulated lymphocytes. In the presence od horse serum, nontoxic doses of the PAO inhibitor 1-hydroxybenzyloxyamine did not affect colony growth of either cell type. However, in the presence of FCS, clonal growth of W 25, ALL, AML, and PHA lymphocytes was significantly stimulated by the enzyme inhibitor. Our data suggest (a) that poor cell proliferation of several tumors in vitro may result from the reaction of polyamines (from cells) and PAO (from serum), (b) that this can be easily tested by means of a specific PAO inhibitor, and (c) that the growth conditions can be optimized by adding nontoxic doses of the enzyme inhibitor or by exchanging FCS for another serum.