Proteasome 20S in multiple myeloma: comparison of concentration and chymotrypsin-like activity in plasma and serum

Abstract

The ubiquitin-proteasome system is relevant in the pathobiology of many haematological malignancies, including multiple myeloma. The assessment of proteasome concentration and chymotrypsin-like (ChT-L) activity might constitute a new approach to diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases. The aim of our study was to determine which material, plasma or serum, is better for measuring chymotrypsin-like (ChT-L) activity and proteasome concentration. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in 70 plasma and serum samples drawn from 28 patients at different treatment stages for multiple myeloma (MM) and 31 healthy volunteers. Proteasome ChT-L activity and concentration in multiple myeloma patients were significantly higher in plasma compared to serum. In this group we observed significant and positive correlations both between the plasma and serum proteasome ChT-L activity and plasma and serum proteasome concentration. The higher values of proteasome concentration and ChT-L activity in plasma than in serum and their better correlations with parameters of tumour load and prognosis suggest that plasma constitutes a better biological material for measuring ChT-L activity and proteasome concentration than serum in multiple myeloma patients.

Application of SPRi Biosensors for Determination of 20S Proteasome and UCH-L1 Levels in the Serum and Urine of Transitional Bladder Cancer Patients

“…The results obtained are consistent with similar previous studies. It has been reported that serum 20S proteasome concentration is elevated in the case of, for example, renal cell carcinoma [37], multiple myeloma [38], breast cancer [39], ovarian cancer [11], and malignant melanoma [40]. Benign conditions, including autoimmune, vascular, and pulmonary conditions, can also alter circulating proteasome levels [41,42].…”

A Peptidomimetic Fluorescent Probe to Detect the Trypsin β2 Subunit of the Human 20S Proteasome

“…Its presence and associated increased enzymatic activity has been observed in several kinds of cancer, including breast tumors [10], prostate cancer [11], head and neck neoplasms [12], and ovarian cancer [7,13].Common examples are patients with multiple myeloma, whose circular 20S proteasome concentrations range between 1.81 and 11.06 µg/mL. However, for healthy people, this value never exceeds 1 µg/mL [14,15]; thus, to facilitate the development of a simple and robust proteasome assay, novel and sensitive tools to study proteasome activity are required.The aim of this work is to develop a new substrate to assay the trypsin-like specificity of the human 20S proteasome that is created by DAPEG building blocks, which are N-substituted functionalized derivates of 3-diaminopropionic acid (Figure 1). The substrate preferences of the β2 subunit have been previously examined [16].…”

“…Common examples are patients with multiple myeloma, whose circular 20S proteasome concentrations range between 1.81 and 11.06 µg/mL. However, for healthy people, this value never exceeds 1 µg/mL [14,15]; thus, to facilitate the development of a simple and robust proteasome assay, novel and sensitive tools to study proteasome activity are required.…”