Figure 6. Osteoclast differentiation is mediated partly through IL-6 secreted by osteolytic PCa.
(A) HSCs derived from osteolytic PC3-bearing animals express endogenous IL-6. HSCs (SLAM or LSK) isolated from tumor bearing animals were analyzed by qRT-PCR to evaluate IL-6 mRNA levels. (B) Effect of IL-6 on osteoclast differentiation. LSK HSCs were isolated from tumor bearing animals and differentiated into osteoclast in the presence or absence of PC3-conditioned medium (PC3-CM) or combination of PC3-CM, RANKL and M-CSF. For blocking studies IL-6 neutralizing antibody (or corresponding control IgG) was added to the treatment groups. Data represent mean ± SD performed in triplicate in 2 independent experiments. The data indicate that IL-6 neutralizing antibody significantly reduced the osteoclast differentiation from HSCs isolated from osteolytic PC3 tumor-bearing animals. (p<0.01 and p<0.001).