Crosstalk between colorectal cancer cells and tumour-associated macrophages

Sammanfattning: Popular Abstract in English Colorectal cancer (CRC) is a cancer caused by uncontrolled cell growth in colon or rectum. CRC is the third most common cancer and the fourth leading cause of cancer related death in the world. It is a multifactorial disease, both genetic predisposition and environmental play a role in the development of CRC. CRC is closely linked to chronic inflammation. Patients with inflammatory bowel disease (IBD) have an increased risk of developing CRC. Tumours are surrounded by the cellular milieu called tumour microenvironment, which is an important hallmark of cancer. In this study, we investigated how colon cancer crosstalk with its microenvironment. Extracellular matrix (ECM) maintains the morphology of cells, as well as mediates various signalling pathways. Under inflammatory or tumoral conditions, remodelling of ECM often occurs. Matrix metalloproteinases (MMPs) are the predominant ECM-degrading enzymes. MMPs and other factors abound in tumour microenvironment alter ECM synthesis and/or selectively cleave ECM domains. These processes can influence cell proliferation and invasion, failure of cell death, and loss of cell differentiation. When cells are exposed to aberrantly expressed ECM proteins, various downstream signalling pathways will be activated. Signals from ECM can be transduced intracellularly by integrins and CD47. In the first article, CD47, associated with integrin, was shown to play a role in ECM mediated cell migration of intestinal epithelial cells. This increased migration was regulated by inflammatory mediator cyclooxygenase-2 (COX-2). Macrophages are important phagocytes involved in host defence. They are also major components of inflammatory tumour microenvironment. Tumour cells can recruit macrophages and change their behaviour. These tumour-associated macrophages (TAMs) perform crosstalk between colon cancer cells via CD47 associated with signal-regulatory protein ! (SIRP!). This association and TAM- derived factors was shown to contribute to colon cancer cell migration. TAM-derived factors can also induce mRNA expression and activity of MMPs in colon cancer cells. This might be one explanation how TAMs can induce colon cancer cell invasion. In summary, these new findings provide an important clue for better understanding of the crosstalk between tumour microenvironment and colon cancers cells, and help to identify new therapeutic targets for colon cancer treatment.