High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma

Abstract

Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs.

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes

“…34 High circulating periostin levels are correlated with reduced bone formation and increased bone resorption. 34 Although recent epidemiological studies indicate that decreased bone mineral density is associated with increased CVD burden, 35,36 the underlying mechanism linking increased POSTN expression with reduced calcification in coronary arteries warrants further investigation. 37,38 The 4 loci previously identified for CAC ( APOB at 2p24.1, 13 PHACTR1 at 6p24.1, 13,14 CDKN2B at 9p21.3, 13,14 and APOE at 19q13.32 13 ) were all associated with coronary artery disease risk, confirming increased CAC as a biomarker of coronary artery disease risk.…”

Pathogenesis of bone disease in multiple myeloma: from bench to bedside

“…Elevated circulating activin A levels have been associated with advanced MM features and adverse prognosis 44 . Increased activin A levels have also been correlated with elevated serum periostin in newly diagnosed MM patients 46 . It has been reported that the crosstalk between BMSCs and MM cells induces activin A secretion 45 .…”

“…Both newly diagnosed and relapsed patients present with elevated levels of periostin in bone marrow plasma and in serum compared to SMM, MGUS, and healthy controls. High periostin levels are also associated with extensive bone lytic lesions, bone fractures and advanced disease characteristics 46 . Interestingly, monoclonal antibodies targeting periostin have emerged with promising results in preclinical models of breast and ovarian cancer 88 ; nevertheless, their role in MM pathogenesis remains to be investigated.…”

Myeloma Bone Disease: The Osteoblast in the Spotlight

“…When sFRP-2 was immunosuppressed, an increase in OB matrix mineralisation was also seen, suggesting sFRP-2 as a potential target for MBD treatment [33], viz., that it is possible to block and reverse its effects. Periostin, a cell-adhesion protein, also inhibits Wnt pathways, with elevated levels in MM associated with osteolysis [73].…”