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Separate Reference From Above
Group Leader: Chris Parish
The major research interest of the Cancer and Vascular Biology Group is the molecular basis of cell adhesion, cell migration and cell invasion, with a particular emphasis on the immune system, tumour metastasis and the growth of new blood vessels (angiogenesis). Of particular focus is the role of anionic carbohyd actrates, such as heparan sulfate (HS), in these processes. The Group is led by Professor Chris Parish, and comprises 3 laboratories, the Cellular Laboratory headed by Chris, the Molecular Mechanisms Laboratory headed by Dr Mark Hulett, and the Matrix Biology Laboratory headed by Dr Craig Freeman.
Role of heparanase in cell invasion and angiogenesis
The BM and ECM are composed of an interlocking network of proteins and complex carbohydrates, and for cells to breach this barrier, they deploy a battery of enzymes that break down these proteins and carbohydrate components.
The major carbohydrate is heparan sulphate (HS), which acts as the glue to maintain the integrity of the BM and ECM. The enzyme responsible for cleaving HS, heparanase, has been shown to play a key role in the degradation of the BM and ECM, and its activity strongly correlates with the metastatic capacity of tumour cells and the migratory capacity of leukocytes and endothelial cells.
HS in the ECM also binds a number of angiogenic growth factors, and the release of these by heparanase promotes angiogenesis and tumour growth. Following our recent cloning of mammalian heparanase, we have been able to develop the tools to investigate how heparanase functions at the molecular level and to directly determine the role of heparanase in cell invasion, angiogenesis and inflammation.
Recently, the group demonstrated that HRG plays an important role in the immune system by interacting with complement components and by preventing the insolubilisation of complexes between antibody and antigen (termed immune complexes). In fact HRG also assists in the uptake of these complexes by phagocytic cells. Thus HRG is probably a key molecule in regulating complement activity and in aiding the elimination of immune complexes from the circulation. In fact, deficiencies in HRG may lead to immune complex-associated diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosis (SLE).
In a related study we have shown that HRG can tether plasmin/plasminogen to the surface of cells and potentially aid cell invasion.
Thus HRG represents a multifunctional protein that appears to play an important role in the immune system, inflammation and wound healing. A major focus of the group in the future is to better understand the functional significance of this intriguing plasma protein.
Development of a novel tumour vaccine
Hulett, M.D., Freeman, C., Hamdorf, B.J., Baker, R.T.,
Harris, M.J. and Parish, C.R. (1999).
Parish CR, Freeman C and Hulett MD (2001)
Freeman, C., Browne, A.M. and Parish, C.R. (1999)
Parish, C.R., Freeman, C., Brown, K.J., Francis, D. and
Cowden, W.B. (1999).
Gorgani, N.N., Parish, C.R., and Altin, J.G. (1999).
Gorgani, N.N., Altin, J.G. and Parish, C.R. (1999).
van Broekhoven, C.L., Parish, C.R., Vassiliou, G. and
Altin, J. (2000).
Hulett MD, Hornby JR, Ohms J, Zeugg J, Freeman C, Gready JE
and Parish CR (2000)
Manderson AP, Pickering MC, Botto M, Walport MJ and Parish
Hindmarsh, E.J., Staykova, M.A, Willenborg, D.O. and
Parish, C.R. (2001)
Armitt, D.J., Banwell, M.G., Freeman, C. and Parish, C.R.
Francis, D.J., Parish, C.R., McGarry,Y. M., Santiago, F.S.,
Brown, K.J., Bingley, J.A., Hayward, I.P., Cowden, W.B., Campbell, J.H.,
Campbell, G.R., Chesterman, C.N. and Khachigian, L.M. (2003)
Mattes, J., Hulett, M., Xie, W., Hogan, S., Rothenberg,
M.E., Foster, P. and Parish, C.R. (2003)
Parish, C.R. (2003)
Wall D, Douglas S, Ferro V, Cowden W and Parish C (2001)
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