Our laboratory has described a
drug-responsive
NADH oxidase activity of the external surface of the plasma membrane of HeLa and other
cancer cells, but not from normal cells, that was shed into
media conditioned by the growth of
cancer cells such as HeLa. The shed form of the activity exhibited the same
drug responsiveness as the plasma membrane-associated form. In this study, sera from
tumor-bearing and control rats,
cancer patients, normal volunteers, and patients with diseases other than
cancer were collected and assayed for a
cancer-specific form of
NADH oxidase responsive to the antitumor sulfonylurea
N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)urea (LY181984). With sera from
tumor-bearing rats and
cancer patients, LY181984 added at a final concentration of 1 microM either inhibited or stimulated the activity. With sera from control rats, normal volunteers, or patients with disorders other than
cancer, the
drug was without effect on the
NADH oxidase activity of the sera. The activity altered by the antitumor sulfonylurea was present both in freshly collected sera and in sera stored frozen. Inhibition was half maximal at about 30 nM LY181984. The sulfonylurea-altered activity was found in sera of nearly 200
cancer patients including patients with solid
cancers (e.g., breast, prostate, lung, ovarian) and with
leukemias and
lymphomas. We postulate that the serum presence of the antitumor sulfonylurea-responsive
NADH oxidase represents an origin due to shedding from the patient's
cancer. If so, the antitumor-responsive
NADH oxidase would represent the first reported cell surface change universally associated with all forms of human
cancer.