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Title: Comparative transcriptomics reveals gain of proliferative capacity in addition to tumor-promoting mechanisms by tumor-associated macrophages in murine chronic lymphatic leukemia      
keywords:
Transcriptome or Gene expression
ID:
PRJNA190087
description:
Tumor-associated macrophages (TAM) are a major component of the tumor microenvironment linked to reduced survival in most tumor entities. Using comparative transcriptomics between macrophages derived from spleen and bone marrow at pre-leukemic and leukemic state, we revealed profound re-programming of macrophages during leukemogenesis neither associated with M1-like nor M2-like macrophage programs. Instead, major transcriptional changes were linked to gain of proliferative capacity and loss of phagocytic mechanisms which we experimentally validated in vivo in mice and in vitro in humans. Using Mif-/- mice as a model for reduced tumor burden and prolonged survival of leukemic mice, we demonstrate that transcriptional programs in TAM are further shaped by such environmental factors enhancing tumorigenic effects. Comparative transcriptomics of macrophages within the same tissue at pre-malignant and malignant state lead to the identification of important macrophage-mediated suppressive mechanisms that can form a basis for the development of novel cancer diagnostics and therapeutics. Overall design: F4/80 macrophages were isolated by FACS-sorting from bone marrow or spleen either prior leukemia or during leukemia in Eµ-TCL1 transgenic mice. In some experiments F4/80+ macrophages were isolated from Mif-/- mice. After the sort, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA190087
authentication:
none
authorization:
none
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject