'Role of bone marrow stromal cells in the growth of human multiple myeloma

Abstract

We have verified the hypothesis that multiple myeloma (MM) may be disseminated by circulating clonogenic cells that selectively home to the bone marrow (BM) to receive the signal(s) leading to proliferation, terminal differentiation, and production of the osteoclast activating factors. Long-term cultures of stromal cells have been developed from the BM of nine patients with MM. These cells were mostly fibroblast- like elements, interspersed with a proportion of scattered macrophages and rare osteoclasts. BM stromal cells were CD54+, produced high levels of interleukin-6 (IL-6) and measurable amounts of IL-1 beta, and were used as feeder layers for autologous peripheral blood mononuclear cells (PBMC). After 3 weeks of cocultures, monoclonal B lymphocytes and plasma cells, derived from PBMC, developed and the number of osteoclasts significantly increased. Both populations grew tightly adherent to the stromal cell layer and their expansion was matched by a sharp increase of IL-6 and by the appearance of IL-3 in the culture supernatant. These data attribute to BM stromal cells a critical role in supporting the growth of B lymphocytes, plasma cells, and osteoclasts and the in vivo dissemination of MM.

Serum YKL‐40 concentrations in newly diagnosed multiple myeloma patients and YKL‐40 expression in malignant plasma cells

“…Gartner and Kaplan (34) showed that the adherent cell layers in murine LTBMCs consist of mononuclear phagocytic cells, endothelial cells and adipocytes. Caligaris-Cappio et al (39) used slightly different culture conditions for human LTBMCs and described the adherent cell layers as fibroblast-like cells interspersed with macrophages and rare osteoclasts. A previous study of skin and fetal lung fibroblasts showed no expression of YKL-40 in these cells in vitro (25) suggesting that the YKL-40 expression seen in the adherent cell layers from LTBMCs are more likely caused by macrophages or osteoclasts.…”

Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement

“…The first data about an expanded pool of OCPs in specific pathologies were published on Paget disease (10). In multiple myeloma, PBMCs from patients with bone lesions gave rise to OCs that resorbed bone in vitro, when cultured in presence of human stromal cells derived from bone marrow (33). The discovery of a pivotal role of RANK, RANKL, and OPG in regulating osteoclastogenesis was substantial for the comprehension of the mechanisms of bone resorption (11-13, 15, 34).…”

Upregulation of osteoblast apoptosis by malignant plasma cells: a role in myeloma bone disease

“…Pathophysiological mechanisms of osteolysis focus on the predominant role of osteoclasts in the formation of myeloma osteolytic lesions (Caligaris-Cappio et al, 1991). The growth of myeloma cells in the experimental severe combined immunodeficiency (SCID) human system, as well as in MM patients, is associated with the increased differentiation of osteoclasts (Yacobby et al, 1998) as a result of their interaction with stromal cells (Chauhan et al, 1996).…”