changes in protein profiles in bortezomib applied multiple myeloma ...
changes in protein profiles in bortezomib applied multiple myeloma ...
changes in protein profiles in bortezomib applied multiple myeloma ...
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of the m<strong>in</strong>eralizations by adjust<strong>in</strong>g the calcium-phosphorus balance. The most<br />
characteristic morphological features of osteoclasts are their curved cell edges and<br />
f<strong>in</strong>ger-shaped cell membrane protrusions. These features makes it easy to form bone<br />
resorption (the destruction of bones from metabolism by melt<strong>in</strong>g physiologically).<br />
function. These two types of cells are controlled various growth factors and they are <strong>in</strong><br />
balance <strong>in</strong> the bone tissues of healthy <strong>in</strong>dividuals. However, this situation is somewhat<br />
differ <strong>in</strong> patients with MM. Because <strong>myeloma</strong> cells change the balance between<br />
osteoblasts (formation of new bones) and osteoclasts (destruction of old bones) <strong>in</strong> favor<br />
of osteoclasts by produc<strong>in</strong>g certa<strong>in</strong> growth factors. While dickkopil, <strong>in</strong>terleuk<strong>in</strong>-3 (IL-3)<br />
and <strong>in</strong>terleuk<strong>in</strong>-7 (IL-7) which are the growth factors secreted by <strong>myeloma</strong> cells are<br />
<strong>in</strong>hibit<strong>in</strong>g the functions of osteoblast cells, macrophage <strong>in</strong>flammatory prote<strong>in</strong> and<br />
<strong>in</strong>terleuk<strong>in</strong>-3 (IL-3) activate the role osteoclast cells either directly or <strong>in</strong>directly (Terpos<br />
and Dimopoulos, 2005; Silvestris et al., 2007; Terpos, 2008) (Figure 1.6). Another<br />
important molecule <strong>in</strong> bone metabolism, RANKL (Receptor Activator for Nuclear<br />
Factor KB Ligand), plays also a role to activate the osteoclasts (Edwards et al., 2008).<br />
In addition to all of these, <strong>myeloma</strong> cells encourage the bone marrow stromal cells to<br />
the production of <strong>in</strong>terleuk<strong>in</strong>-6 (IL-6), <strong>in</strong>terleuk<strong>in</strong>-1 (IL-1) and Tumor Necrosis Factor<br />
(TNF) to <strong>in</strong>crease osteoclast formation and tumor growth (Sirohi and Powles, 2004;<br />
Terpos, 2008; Roodman, 2009). These <strong>in</strong>terleuk<strong>in</strong>s activates <strong>multiple</strong> pathways that<br />
protect <strong>myeloma</strong> cells from apoptosis (Zaidi and Vesole, 2001; Bommert et al., 2006).<br />
Figure 1.6. Tumor-micro Environmental Interactions <strong>in</strong> MM<br />
(Source: Roodman, 2009)<br />
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