Metastases and multiple myeloma generate distinct transcriptional footprints in osteocytes in vivo.

Osteocytes are the most abundant bone cells, playing important roles in tissue maintenance. Little is known of how they react in vivo to cancer stress. Here we present a comparative study of the effect of a bone-residing tumour (myeloma) and metastases of bone-remote cancers on osteocytes. While no differences in morphology of the bone are seen, the changes in the transcriptome of osteocytes are specifically related to the tumour stress present. Screening approximately 22 000 genes in osteocytes prepared from cryosections of native bone using laser-supported microdissection, we observed approximately 1400 and approximately 1800 gene expression differences between osteocytes dissected from normal bone compared with those associated with metastases and multiple myeloma, respectively. The genes up-regulated due to the stress exerted by metastases were repressed by multiple myeloma and vice versa, indicating stress-specific footprints in the transcriptome of osteocytes. Functionally, the stressors seem to impose selective pressures on signalling pathways such as that of TGFbeta, a major player in bone biology. Our data show for the first time that the transcriptome of osteocytes in vivo becomes strongly affected by cancer stress, generating gene expression footprints which, in contrast to comparable morphological changes, appear to relate to the nature of cancer and might thus become helpful in distinguishing different bone diseases.