Transcription profiling of multiple mouse myeloma (MM) cells during intra-medullary progression in the 5T2MM mouse model

Insights into mechanisms involved during intra-medullary myeloma progression could be helpful in the better understanding of this disease and in the development of new therapeutical strategies. Herein gene expression profile of multiple myeloma (MM) cells during intra-medullary progression was investigated using the 5T2MM murine model. MM-cells from 3 subsequent disease stages, quiescent, intermediate and end stage were analyzed using microarrays containing 21,492 Unigene cDNA sequences. ~ 3000 calls of differentially expressed genes were obtained. Most of these genes were silenced during tumor progression. In the early stage the MM-cells had up-regulated genes involved in bone marrow (BM) homing (CCR2, CCR5), motility (tetraspanins, 67kD laminin receptor, paxillin, zyxin, prolactin receptor), invasion (annexin II, cathepsins), adhesion (integrins, ALCAM) and cell adhesion mediated drug resistance (fibronectin). Genes involved in apoptosis (Mcl-1), plasma cell differentiation (XBP-1), angiogenesis (neuropilin-2, angiopoietin-like 4), hypoxia (HIF-1a, carbonic anhydrase 9) and in retention (CXCR4/CXCL12) and anchoring of MM-cells (laminin, collgens) in the BM were up-regulated during progressive stages. Quantative RT-PCR confirmed the trend of expression. These data provide a framework of mechanisms involved in intra-medullary myeloma progression; several genes known to be important in MM-biology are highlighted and novel candidate genes are illuminated as potentially more effective therapeutical targets.