MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages. Br J Haematol 2013 Mar;160(6):779-84
Date
12/21/2012Pubmed ID
23252623Pubmed Central ID
PMC3594344DOI
10.1111/bjh.12175Scopus ID
2-s2.0-84874705979 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Benefit from cytotoxic therapy in myeloma may be limited by the persistence of residual tumour cells within protective niches. We have previously shown that monocytes/macrophages acquire a proinflammatory transcriptional profile in the myeloma microenvironment. Here we report constitutive activation of MAP3K8 kinase-dependent pathways that regulate the magnitude and extent of inflammatory activity of monocytes/macrophages within myeloma niches. In myeloma tumour cells, MAP3K8 acts as mitogen-induced MAP3K in mitosis and is required for TNFα-mediated ERK activation. Pharmacological MAP3K8 inhibition results in dose-dependent, tumour cell-autonomous apoptosis despite contact with primary stroma. MAP3K8 blockade may disrupt crucial macrophage-tumour cell interactions within myeloma niches.
Author List
Hebron E, Hope C, Kim J, Jensen JL, Flanagan C, Bhatia N, Maroulakou I, Mitsiades C, Miyamoto S, Callander N, Hematti P, Asimakopoulos FAuthor
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
HumansMAP Kinase Kinase Kinases
Macrophages
Monocytes
Multiple Myeloma
Neoplasm, Residual
Protein Kinase Inhibitors
Proto-Oncogene Proteins
Tumor Cells, Cultured