Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored.
Interestingly, modulation of PPARG activity within the bone marrow microenvironment has been recently shown to interfere with cytokines such as IL6, which is involved with a central role in the pathogenesis of MM (Wang et al, 2004), suggesting also that PPARG may represent a valuable therapeutic target in MM (Garcia-Bates et al, 2008).
The relationship between the number of osteoblasts, bone formation, and minimal development of hematopoietic microenvironment has been described previously [ 22, 29].
Several factors produced in the bone stromal microenvironment have been shown to promote chemotactic migration, including insulin-like growth factors, platelet-derived growth factor (PDGF) and stromal cell derived factor 1 (sdf-1/CXCL12) [ 45, 54- 56].
The same experiments were performed on B-CLL cells co-cultured with mesenchymal stromal cells (MSCs) from healthy donors, since MSCs of the bone marrow microenvironment have been reported to protect B-CLL cells from apoptosis induced by conventional chemotherapeutics.
Numerous factors, known to be present in the bone-tumor microenvironment, have been shown to induce MCP-1 secretion and gene expression including MCP-1 itself [ 39], TGF-β [ 40, 41], tumor necrosis factor-alpha (TNF-α) [ 42], parathyroid hormone related peptide (PTHrP) [ 39] and various interleukins [ 43, 44].
This may also mimic a consolidation of bone fracture gaps, despite the fact that the distribution of the bone properties in such microenvironments has been poorly elucidated.
While this interaction occurs largely in the bone microenvironment, it has been shown that monocytes from the spleen, peripheral blood, and synovium are all capable of RANKL-dependent osteoclast formation [ 8].
In recent years, the idea that osteolytic bone metastasis is driven by intricate cellular and molecular interactions among tumor cells and the host stromal cells commonly found in the bone microenvironment has drawn much attention.
