The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients

Abstract

Background: Osteolytic bone disease is a major hallmark in multiple myeloma (MM) progression and affects many patients. Several inflammatory cells are involved in MM progression. Among them, mast cells (MCs) accumulated in the bone marrow (BM) microenvironment are known to play an important role in the mechanism of neovascularization. Methods: In 52 newly diagnosed active MM patients, we measured BM MC density (MCD) using an immunohistochemical stain for tryptase, serum levels of matrix metalloproteinase-9 (MMP-9) and receptor activator of nuclear factor κB ligand (RANKL) by a solid-phase sandwich enzyme-linked immunosorbent assay, along with urine levels of N-terminal propeptide of procollagen type I (Ntx) by a competitive inhibition enzyme-linked immunosorbent assay, in various clinical stages and skeletal grades. Results: MCD, RANKL and Ntx were higher in MM patients. All values increased in association with both the clinical stage and skeletal grade. Furthermore, MCD correlated positively with MMP-9, RANKL and Ntx. Conclusions: Our data suggest that MCs may contribute to osteolytic processes during MM progression. Although the major role of MCs in tumor progression is to enhance angiogenesis, it seems that they may affect MM bone disease and may secrete a plethora of mediators that may directly and indirectly have an impact on osteolysis.

Mast Cells, Angiogenesis and Lymphangiogenesis in Human Gastric Cancer

“…Mast cells in human tumour were initially described by Paul Ehrlich and extended by Eugen Westphal [68]. Tumour-associated mast cells (TAMCs) are a component of the microenvironment of nearly all solid [49,69,70,71,72,73,74,75,76,77,78,79,80,81,82] and haematologic human tumours [83,84,85,86,87,88,89,90,91,92,93]. TAMCs may exert pro- or anti-tumorigenic roles depending on but not limited to, the tumour model, the stage and the type of tumour and their localization within the tumour (i.e., intra-tumoral vs peri-tumoral) [35,94].…”

Human mast cells and basophils—How are they similar how are they different?

“…Mast cells were first identified in human tumors by Ehrlich and their role was extended by Westphal . Tumor associated mast cells (TAMCs) are present in the tumor microenvironment (TME) of a plethora of human solid and hematologic tumors . Peritumoral and/or intratumoral mast cells are increased in different human cancers attracted by tumor‐derived chemotactic factors such as SCF, VEGFs, Ang1, CXCL8/IL‐8, CCL2, CXCL1, and CXCL10 …”

“…405 Tumor associated mast cells (TAMCs) are present in the tumor microenvironment (TME) of a plethora of human solid 252,[406][407][408][409][410][411][412][413][414][415][416][417][418][419] and hematologic tumors. [420][421][422][423][424][425][426][427][428] Peritumoral and/or intratumoral mast cells are increased in different human cancers 61 attracted by tumor-derived chemotactic factors such as SCF, 25,429 VEGFs, 252 Ang1, 219 CXCL8/IL-8, 253 CCL2, CXCL1, and CXCL10. 252,409 In several tumors such as thyroid, 252,253 gastric, [430][431][432][433] pancreas, 411,[434][435][436][437][438] and bladder cancers, 439 and Merkel cell carcinoma 407 TAMCs always appear to be pro-tumorigenic.…”

Mast Cells and Angiogenesis in Human Plasma Cell Malignancies

“…Vyzoukaki et al [83,84] demonstrated that bone marrow mast cell density in MM patients is correlated with radiographic skeletal grades and evaluated serum levels of Ang-2 and MMP-9 and found them to be positively correlated with bone marrow mast cell density in patients with active MM.…”