Wilms' tumor clinical correlation with circulating mucin in three cases

Abstract

Three children with Wilms' tumors have been shown to contain an abnormal mucin, or protein‐polysaccharide complex, in their serum, urine, and in cell‐free tumor extracts. This material appears to be a complex polymer of hexosamine and uronic acid with protein, and has an unusually low isoelectric point. Detection of the protein‐polysaccharide complex in the blood is correlated with the clinical stage of growth of the Wilms' tumor and the appearance of recurrent metastases. During those periods of time when the children were clinically free of disease, no abnormal protein‐polysaccharide complex could be identified in serum or urine samples. However, when the tumor recurred, this material increased in concentration and became maximal during terminal stages of the disease. Detecting the presence of this material has been shown to be particularly useful in improving diagnosis and long‐term care of these children with Wilms' tumor. Studies in our own laboratories and elsewhere suggest strongly that this material is a secretion product of the tumor itself. The finding of a tumor‐derived protein‐polysaccharide complex in patients with Wilms' tumor adds this disorder to the growing list of functioning secretory malignant tumors.

Glycosaminoglycan Synthesis by Wilms' Tumor

“…Similar levels of hyaluronic acid in the serum and urine of Wilms' tumor patients have been reported by others (4,7,21,24,29).…”

“…The finding that hyaluronic acid is present in high concentrations in serum, urine, and the tumor and that surgical removal of the tumor results in the disappearance of hyaluronic acid from the serum of these patients (24), has provided only circumstantial evidence that the circulating hyaluronic acid is synthesized by the tumor. The evidence reported in the present paper shows directly that hyaluronic acid and chondroitin sulfate are synthesized at very high levels in minced tissue, cultured cells, and cell-free preparations from Wilms' tumor.…”

“…Powars et al (24) have speculated that hyaluronic acid may be involved in the growth and control of metastasis of Wilms' tumor. Beierle et al (2) have reported that the serum of patients with Wilms' tumor or a crude glycosaminoglycan fraction isolated from Wilms' tumor selectively enhances the growth of cultured kidney or lung cells.…”

“…On the last day of culture, cells were suspended in 1 0 ml Modified Eagle's medium ( l a ) , fetal calf, calf serum, and medium and incubated for 24 Varidase, used as a source of streptococcal hyaluronidase Two g Wilms' tumor were finely minced and incubated for 8 (1 l ) , was obtained from Lederle Laboratories. Testicular hya-hr at 37" with 5 ml modified Eagle's medium, 1 ml Hanks' luronidase (20,000 IU/mg) was purchased from Leo-Helsinborg balanced salt solution, 300 pCi H235S04, and 300 pCi Laboratories, Sweden, and chondroitinase ABC and pig skin [3H]acetate.…”

Proteoglycans and neoplasia

“…Moreover, tumor tissue or cells derived from Wilms' tumors synthesize high levels of hyaluronic acid [39]. Following surgical removal of the affected kidney, the blood levels of hyaluronic acid, which can reach peaks of 0.2 mg/ml, fall dramatically to normal levels [40]. These findings strongly indicate that Wilms' tumors synthesize and release large amounts of this polysaccharide in vivo.…”