Connective tissue components in serum in multiple myeloma: Analyses of propeptides of type I and type III procollagens, type I collagen telopeptide, and hyaluronan

Abstract

The present study was performed to evaluate whether information concerning synthesis and degradation of type I collagen in multiple myeloma (MM) as obtained by serum analyses of C-terminal propeptide of type I procollagen (PICP) and the C-terminal telopeptide of type I collagen (ICTP) may be useful in evaluating the development of osteolytic bone destruction. Serum N-terminal propeptide of type III procollagen (PIIINP) may give information about marrow fibrosis in MM. No data are available about MM and serum hyaluronan, another important component of bone marrow stroma. We examined 15 consecutive patients before treatment and 15 sex- and age-matched controls. We found highly significant elevations in serum ICTP (median 6.2 vs. 2.4 micrograms/L; P < 0.01), PIIINP (median 5.2 vs. 2.9 micrograms/L; P < 0.01) and hyaluronan (median 122 vs. 45 micrograms/L; P < 0.01). ICTP in serum correlated closely to bone morbidity (r = 0.69; P < 0.01). Furthermore, serum ICTP correlated highly significantly to serum PIIINP (P < 0.01) and serum beta 2-microglobulin (P < 0.01), whereas there was no correlation between hyaluronan and any of the collagen-derived peptides or beta 2-microglobulin. The MM group was followed for 9-25 months and analysis of survival data suggested that serum ICTP may be of predictive value (P < 0.05). We conclude that important changes in connective tissue metabolism occur in MM. ICTP in serum seems to be a noninvasive marker of bone morbidity and may be of prognostic value. Furthermore, elevation of hyaluronan in serum is common in MM, the significance of which is unknown.

Bone marrow fibrosis and disease activity in multiple myeloma monitored by the aminoterminal propeptide of procollagen III in serum

“…By immunohistochemistry the fibrous tissue in plasma cell infiltrated areas can be stained with antibodies against the aminoterminal propeptide of type III procollagen (Taube et al, 1992), indicating that collagen type III may be the major collagen subtype involved in this interstitial fibrosis, as described in primary idiopathic myelofibrosis (Apaja-Sarkkinen et al, 1986;Lisse et al, 1991). Moreover, we and others have found elevated serum concentrations of the aminoterminal propeptide of type III procollagen (PIIINP) in MM (Taube et al, 1992;Abildgaard et al, 1994Abildgaard et al, , 1997, and the use of serum PIIINP as a non-invasive indicator of bone marrow fibrogenesis and myeloma activity has been suggested (Taube et al, 1992). However, pre-treatment serum PIIINP has no prognostic value (Abildgaard et al, 1997).…”

Characterization of hyaluronan synthase expression and hyaluronan synthesis in bone marrow mesenchymal progenitor cells: predominant expression of HAS1 mRNA and up-regulated hyaluronan synthesis in bone marrow cells derived from multiple myeloma patients

“…5 In particular, hyaluronan production is up-regulated in a variety of malignant tissues compared with normal cells, and increased hyaluronan levels have been shown to correlate with increased tumor cell invasion, migration, and proliferation. [6][7][8] A role for hyaluronan in multiple myeloma pathophysiology has recently been suggested, where abnormally high or low serum hyaluronan has been correlated with poor prognosis, 9,10 conveying the prognostic importance of this molecule. Multiple myeloma is a malignancy characterized by the accumulation of malignant plasma cells within the bone marrow, wherein soluble factors and cell-cell contact likely provide optimal conditions for proliferation and survival.…”

Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy‐terminal telopeptide of type I collagen (ICTP)

“…In metabolic bone diseases serum levels of ICTP have been shown to correlate with bone resorption rate estimated both histomorphometrically and by calcium kinetic studies (Eriksen et al, 1993;Charles et al, 1994). Recently we and others have published data suggesting a prognostic value of serum ICTP in multiple myeloma (Abildgaard et al, 1994;Elomaa et al, 1992). Collagen type I is synthesized by the osteoblasts as a procollagen precursor with non-helical aminoacidic extensions, propeptides, at either end.…”

“…Marrow fibrosis and angiogenesis are seen in multiple myeloma and have prognostic implications (Krzyzaniak et al, 1988;Vacca et al, 1994). Recent studies have proposed the use of PIIINP in serum in the management of multiple myeloma (Taube et al, 1992b;Abildgaard et al, 1994).…”