E-MEXP-186 - Transcription profiling of multiple mouse myeloma (MM) cells during intra-medullary progression in the 5T2MM mouse model
Released on 27 March 2008, last updated on 2 May 2014
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.
transcription profiling by array, dye swap, loop
Paul Van Hummelen <firstname.lastname@example.org>, Benjamin Van Camp, Ivan Van Riet, Karin Vanderkerken, Kewal Asosingh, Marnik Vuylsteke
Gene expression profiling of 5T2MM murine myeloma cells during intra-medullary tumor progression. Kewal Asosingh; Marnik Vuylsteke; Ivan Van Riet; Benjamin Van Camp; Karin Vanderkerken; Paul Van Hummelen.