CONSTITUTIVE SECRETION OF SOLUBLE INTERLEUKIN-2 RECEPTOR BY HUMAN T-CELL LYMPHOMA XENOGRAFTED INTO SCID MICE - CORRELATION OF TUMOR VOLUME WITH CONCENTRATION OF TUMOR-DERIVED SOLUBLE INTERLEUKIN-2 RECEPTOR IN BODY-FLUIDS OF THE HOST MICE

Increased serum concentration of soluble ct-chain receptor for interle ukin-2 (sIL-2R) has been noted inpatients with a variety of inflammato ry conditions and lymphoid malignancies including T cell leukemia and lymphoma. Elevated sIL-2R serum levels seen in lymphoid malignancies a ppear to correlate with the clinical stage of disease. However, becaus e sIL-2R is produced by normal activated lymphocytes, it has been unce rtain whether serum sIL-2R in such conditions is derived from tumor ce lls or normal immune cells responding to the tumor. To address this qu estion, we used a model of human (CD30(+)) anaplastic, large T cell ly mphoma transplanted into immunodeficient SCID mice. Reverse transcript ion polymerase chain reaction of tumor RNA showed that the tumor, desi gnated mJB6, contains mRNA for alpha-chain of human IL-2R. Furthermore , 15 to 25% of tumor cells stained with anti-human IL-2R alpha-chain m Ab. Solid phase ELISA analysis of serum samples from mice bearing mJB6 lymphoma showed high concentrations of human sIL-2R. None of the cont rol mice without lymphoma or with human nonlymphoid tumors (prostatic carcinoma, ovarian carcinoma, and glioblastoma multiforme) showed dete ctable human sIL-2R. The sIL-2R serum titers of mJB6-bearing mice cor- related strongly with tumor volume (P < 0.0001). Tumors as small as 0. 4 to 0.8 mm(3) could be detected by this method. The sensitivity of sI L-2R ELISA exceeded at least 150 times the sensitivity of conventional radioisotopic tumor detection. Total resection of mJB6 tumors resulte d in complete clearance of sIL-2R from the murine serum within 48 hour s with a half-life of 6 hours. Accordingly, partial resection led to a significant decrease in sIL-2R followed by gradual increase with tumo r regrowth, sIL-2R was also detected in the urine of mJB6-transplanted mice. As in serum, urine concentrations of sIL-2R were proportional t o tumor mass (P < 0.02). Based on these findings we postulate that mal ignant cells are a major source of serum sIL-2R in patients with lymph oid tumors. In addition, our data further support monitoring sIL-2R co ncentration in body fluids as a sensitive method to detect change in t umor volume in such patients.