SOCS regulate macrophage polarisation : importance in cancer development

• Main Author: Fitzsimons, Amy
• Published: Queen's University Belfast 2013
• Subjects: 616.994061
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.601476

Macrophages (M0s) which can have a profound impact on tumour growth and are broadly classified into two subsets: 1) Inflammatory, tumoricidal "classically activated" Ml M0s or anti-inflammatory, pro-tumour "alternatively activated" M2 M0s. High M2 M0 density within tumours is associated with poor prognosis in patients. sacs proteins attenuate cytokine signalling via the JAKJSTA T pathway, and therefore regulate inflammatory responses. Our findings indicate that deletion of Socs2 and Socs3 genes in mice alter M0 subset homeostasis and polarisation towards Ml or M2 subsets, respectively. Opposing M0 subsets observed in these mice resulted in divergent tumour growth rates in both in a chemically inducible model of squamous cell carcinoma (SCC) and a syngeneic murine colorectal adenocarcinoma model Adoptive transfer FACS sorted bone SOCS2/3-null monocytes into WT tumour bearing mice resulted in similar trends in tumour growth are transferrable. Myeloid restricted deletion of SaCS3 in mice results in accelerated tumour growth accompanied by enhanced angiogenesis, and macrophage infiltration. These findings suggest that SOCS proteins have a profound influence on macrophage polarization and consequently tumour growth. Targeting SOCS proteins may be a viable therapeutic target in treatment of cancer.