September 28, 2011 -- Study points to the need to relook at current cancer therapies that target the body’s immune system
1. Scientists at A*STAR’s Singapore Immunology Network (SIgN) have shown for the first time that PMN-MDSC, a type of immune cell in the body that suppresses the immune response, can actually accelerate the growth and spread of cancerous tumours directly. This finding explains how inflammation, the body's natural defence mechanism when a tissue or an organ becomes affected, is linked to cancer progression. It also highlights the need for a careful reassessment of current cancer therapies that target the body’s immune system to combat cancer.
2. Using a mouse model of melanoma, one of the most aggressive types of skin cancer, Benjamin Toh, an A*STAR scholar working under the supervision of Professor Jean-Pierre Abastado, a Principal Investigator of SIgN, discovered that the primary tumour first produces a unique protein “CXCL5”. CXCL5 specifically attracts the PMN-MDSC immune cells to the primary tumour, accelerating its growth. These PMN-MDSC immune cells also reactivate an innate cellular programme in early skin growth, which causes the cancer cells to detach and spread from the primary tumour to other parts of the body. However, this migratory ability is transient; migrating cancer cells can spontaneously lose their migratory potential and form a new tumour in another site.
3. Said Prof Abastado, “We are really excited because our finding is a clear mechanistic explanation for the long-recognized link between inflammation and cancer progression. It may have significant and far-reaching clinical implications in the way we treat cancer. This study will certainly prompt us to re-think about cancer therapies that aim at boosting the immune system.”
4. This latest finding on the cancer cells’ transient migratory ability also reinforced the team’s earlier studies which showed that cancer cells can in fact detach and migrate away from the primary tumour at a very early stage, often before the primary tumour is even detected. This challenges the current theory that cancer progression is a linear process, where the developing cancer cell sequentially accumulates mutations that give it the ability to metastasize i.e. to migrate from the primary tumour and settle in a new site to establish a new tumour.
5. Prof Paola Castagnoli, Scientific Director of SIgN added, “This study has definitely opened a new area in cancer research where more specific therapeutic targets might be uncovered within our body’s immune system. It is such new knowledge discovered through fundamental research that we are able to find new strategies to combat complex clinical conditions like cancer with a more holistic and effective approach.”
The research findings described in this news release can be found in the 27 Sept 2011 issue of PLoS Biology under the title, "Mesenchymal Transition and Dissemination of Cancer Cells is driven by Myeloid-Derived Suppressor Cells infiltrating the Primary Tumour” by Benjamin Toh1, Xiaojie Wang1, Jo Keeble1, Wen Jing Sim2, Karen Khoo1, Wing-Cheong Wong4, Masashi Kato5, Armelle Prevost-Blondel6, Jean-Paul Thiery2,3 and Jean-Pierre Abastado1
1 Singapore Immunology Network (SIgN), BMSI, A*STAR, Singapore
2 Institute for Molecular and Cellular Biology (IMCB), BMSI, A*STAR, Singapore
3 Cancer Science Institute, National University of Singapore
4 Bioinformatics Institute (BII), BMSI, A*STAR, Singapore
5 College of Life and Health Sciences, Chubu University, Aichi, Japan
6 Institut Cochin, Université Paris Descartes, CNRS UMR 8104, Paris, France.
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About the Singapore Immunology Network (SIgN)
The Singapore Immunology Network (SIgN), officially inaugurated on 15 January 2008, is a research consortium under the Agency for Science, Technology and Research (A*STAR)’s Biomedical Research Council. The mandate of SIgN is to advance human immunology research and participate in international efforts to combat major health problems. Since its launch, SIgN has grown rapidly and currently includes 200 scientists from 25 different countries around the world working under 20 renowned principal investigators. At SIgN, researchers investigate immunity during infection and various inflammatory conditions including cancer and are supported by cutting edge technological research platforms and core services.
Through this, SIgN aims to build a strong platform in basic human immunology research for better translation of research findings into clinical applications. SIgN also sets out to establish productive links with local and international institutions, and encourage the exchange of ideas and expertise between academic, industrial and clinical partners and thus contribute to a vibrant research environment in Singapore. For more information about SIgN, please visit www.sign.a-star.edu.sg.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.
A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners.
For more information about A*STAR, please visit www.a-star.edu.sg.