Wasik M A, Sioutos N, Tuttle M, Butmarc J R, Kaplan W D, Kadin M E
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts.
Am J Pathol. 1994 May;144(5):1089-97.
Increased serum concentration of soluble alpha-chain receptor for interleukin-2 (sIL-2R) has been noted in patients with a variety of inflammatory conditions and lymphoid malignancies including T cell leukemia and lymphoma. Elevated sIL-2R serum levels seen in lymphoid malignancies appear to correlate with the clinical stage of disease. However, because sIL-2R is produced by normal activated lymphocytes, it has been uncertain whether serum sIL-2R in such conditions is derived from tumor cells or normal immune cells responding to the tumor. To address this question, we used a model of human (CD30+) anaplastic, large T cell lymphoma transplanted into immunodeficient SCID mice. Reverse transcription polymerase chain reaction of tumor RNA showed that the tumor, designated 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 mAb. Solid phase ELISA analysis of serum samples from mice bearing mJB6 lymphoma showed high concentrations of human sIL-2R. None of the control mice without lymphoma or with human nonlymphoid tumors (prostatic carcinoma, ovarian carcinoma, and glioblastoma multiforme) showed detectable human sIL-2R. The sIL-2R serum titers of mJB6-bearing mice correlated strongly with tumor volume (P < 0.0001). Tumors as small as 0.4 to 0.8 mm3 could be detected by this method. The sensitivity of sIL-2R ELISA exceeded at least 150 times the sensitivity of conventional radioisotopic tumor detection. Total resection of mJB6 tumors resulted in complete clearance of sIL-2R from the murine serum within 48 hours with a half-life of 6 hours. Accordingly, partial resection led to a significant decrease in sIL-2R followed by gradual increase with tumor regrowth. sIL-2R was also detected in the urine of mJB6-transplanted mice. As in serum, urine concentrations of sIL-2R were proportional to tumor mass (P < 0.02). Based on these findings we postulate that malignant cells are a major source of serum sIL-2R in patients with lymphoid tumors. In addition, our data further support monitoring sIL-2R concentration in body fluids as a sensitive method to detect change in tumor volume in such patients.
在患有各种炎症性疾病和淋巴系统恶性肿瘤（包括T细胞白血病和淋巴瘤）的患者中，已观察到血清中白细胞介素-2可溶性α链受体（sIL-2R）浓度升高。在淋巴系统恶性肿瘤中观察到的sIL-2R血清水平升高似乎与疾病的临床分期相关。然而，由于sIL-2R由正常活化的淋巴细胞产生，因此尚不确定在此类情况下血清sIL-2R是来源于肿瘤细胞还是对肿瘤作出反应的正常免疫细胞。为了解决这个问题，我们使用了将人（CD30+）间变性大T细胞淋巴瘤移植到免疫缺陷SCID小鼠体内的模型。肿瘤RNA的逆转录聚合酶链反应表明，名为mJB 的肿瘤含有人类IL-2Rα链的mRNA。此外，15%至25%的肿瘤细胞被抗人IL-2Rα链单克隆抗体染色。对携带mJB6淋巴瘤的小鼠血清样本进行的固相ELISA分析显示，人sIL-2R浓度很高。没有淋巴瘤或患有人类非淋巴肿瘤（前列腺癌、卵巢癌和多形性胶质母细胞瘤）的对照小鼠均未检测到可检测到的人sIL-2R。携带mJB6的小鼠的sIL-2R血清滴度与肿瘤体积密切相关（P<0.0001）。用这种方法可以检测到小至0.4至0.8立方毫米的肿瘤。sIL-2R ELISA的灵敏度至少超过传统放射性同位素肿瘤检测灵敏度的150倍。mJB6肿瘤的完全切除导致小鼠血清中的sIL-2R在48小时内完全清除，半衰期为6小时。因此，部分切除导致sIL-2R显著下降，随后随着肿瘤再生而逐渐增加。在移植了mJB6的小鼠尿液中也检测到了sIL-2R。与血清中一样，尿液中sIL-2R的浓度与肿瘤大小成正比（P<0.02）。基于这些发现，我们推测恶性细胞是淋巴肿瘤患者血清sIL-2R的主要来源。此外，我们的数据进一步支持监测体液中sIL-2R浓度作为检测此类患者肿瘤体积变化的一种灵敏方法。
