A team from the Metastasis Research Laboratory (GIGA-Cancer/Liège University Hospital) has just published their work demonstrating that the DMP1 protein has previously unsuspected anti-angiogenic activities which could be used for the development of new treatments against cancer, but also against diseases in which angiogenesis (the formation of new blood vessels) plays a major role, such as psoriasis, rheumatoid arthritis, or diabetic retinopathy.
This discovery has also led to the registering of a patent by the three research protagonists: Dr. Akeila Bellahcène, a Senior Research Associate at the National Fund for Scientific Research (NFSR) who is running the project, Sophie Pirotte, a TELEVIE (NFSR) researcher, and Professor Vincent Castronovo, the Laboratory's Director.
Dr. Bellahcène has been interested in SIBLINGs proteins for several years. They are a family of glycoproteins initially discovered for their role in the formation of bones and teeth. It is now over 15 years ago that the Liège laboratory was the first to show that two of these proteins, bone sialoprotein (BSP) and osteopontin (OPN), are produced by cancer cells and probably play a role in the progression of these cancers, notably through their involvement in the formation of bone metastases. These original observations, confirmed by other international teams, opened the way for numerous projects studying the role played by these two proteins in cancer. Up until recently, DMP1, known above all for its role in teeth mineralization, had not attracted attention in terms of a role in the development and progression of cancer.
But Dr. Akeila Bellahcène's most recent research demonstrates that DMP1 also deserves very special attention. In effect the results published show that DMP1 is capable of blocking angiogenesis. Yet angiogenesis is vital for the development of tumors beyond a few cubic millimeters, as well as for the formation of metastases.
The work shows that DMP1 prevents endothelial cells (the cells which form new blood vessels over the course of angiogenesis) to respond to VEGF, a molecular signal sent by cancer cells to activate the formation of new feeder blood vessels. The presence of DMP1 halts the different stages which lead to the formation of new capillaries: the endothelial cells are placed in a resting non-proliferative state.
"In an in vivo model of angiogenesis linked to tumor development, we have shown that the tumors from cancer cells in which we had beforehand overexpressed DMP1 had a reduced growth combined with very modest vascularization in comparison with the control tumors," points out Dr. Bellahcène.
"These results overall indicate that DMP1 could represent a new anti-angiogenesis molecule whose therapeutic implications would moreover go beyond their use in cancer pathology," states Professor Vincent Castronovo, who directs the Metastasis Research Laboratory at the ULg's GIGA-ResearchUnit. "In effect the processes of angiogenesis induced by VEGF also intervene in a significant manner in the development and progression of other pathologies such as rheumatoid arthritis, psoriasis, and diabetic retinopathy."
Illustration: Microsoft clipart.
Science Daily (01/27/11)
Abstract (Blood; Vol. 117, No. 8, 2515-2526 (02/24/11))