Effect of plasma inter-alpha trypsin inhibitor and cancer-related glycoprotein EDC1 on phytohemagglutinin-induced thymidine uptake in lymphocytes.

EDC1, a glycoprotein with a molecular weight of 27,500, was purified from the urine of a leukemic patient, and a radioimmunoassay was developed to use as an immunodiagnostic tool for cancer. Previous studies showed that up to 60% of patients with disseminated neoplastic diseases excreted 100 to 500 mg of EDC1 per day. This protein was immunologically related to inter-alpha-trypsin inhibitor (IATI; M.W. 170,000), a glycoprotein normally present in plasma. EDC1, like IATI, inhibited trypsin and chymotrypsin. EDC1 and IATI have now been found to inhibit the incorporation of thymidine into DNA of normal lymphocytes transformed by phytohemagglutinin. In the presence of 1000 micrograms of EDC1 or 300 micrograms of IATI, incorporation of thymidine by cells was totally inhibited. These proteins were not cytotoxic, did not affect transport of thymidine across the membrane, formed no complex with phytohemagglutinin, and did not compete with phytohemagglutinin for its binding sites. It is proposed that EDC1 and IATI may exert this effect by inhibiting a protease required for blastogenesis.