Published: 16 August 2005

Project leader: Dr. Shoukat Dedhar – BC Cancer Agency, Vancouver, B.C.

Modules for the identification of novel molecular targets and therapeutics for organ-specific metastasis of breast cancer

Death from breast cancer is usually caused by the spread of cancer cells from the primary breast tumor to the rest of the body, a process called metastasis.  The later breast cancer is detected, the greater the risk that metastatic spread has occurred.  The development of new therapies against breast cancer has largely focused on the treatment of the primary tumor and not on inhibiting the growth of metastatic cells in specific organs.  This is mainly due to our current lack of understanding of why breast cancer cells thrive in the microenvironment of certain organs, such as bone. Dr. Dedhar and his team propose to create new experimental models using laboratory-grown cancer cells and genetically modified mice, and to develop new imaging and gene and protein analysis technologies.  This will enable them to identify and characterize genes and proteins that are crucial for the growth of breast cancer metastases in different organs. The program is designed to generate synergistic interactions between the team members, resulting in the accelerated development of novel therapies specifically targeted against metastases and the identification of new tools for diagnosis and more accurate prognosis of metastatic breast cancer.

Component projects

Dr. Shoukat Dedhar - Cancer Genetics, BC Cancer Agency, Vancouver, B.C

Models for the identification and characterization of organ-specific gene and protein expression in metastatic breast cancer cells

Treatment of metastatic breast cancer often fails because of our lack of understanding of the genes and proteins that control metastatic growth and survival of breast cancer cells.  In this project, Dr. Dedhar will use laboratory-grown cancer cells and genetically modified mice to study the genes and proteins produced by metastatic cancer cells growing in the liver, lung and bones. This mouse model will use live imaging technology to follow the growth of metastases in different organs. He will compare these genes and proteins to those produced by the primary tumor growing in the breast and among different sites of metastatic growth.  He will also compare these genes and proteins to those expressed in the tissue surrounding the primary tumor.  These genes and proteins may represent potential novel targets for new treatment as well as new diagnosis and prognosis indicators for metastatic breast cancer.

Dr. Christopher Overall - Oral Biological and Medical Sciences, Faculty of Dentistry, UBC, Vancouver, B.C; Canada Research Chair in Metalloproteinase Proteomics and Systems Biology

Proteomic and degradomic analysis of breast cancer metastases

One of the ways that breast cancer spreads and invades distant organs in the body, a process called metastasis, is by dissolving the tissues surrounding the tumors using enzymes called proteases.  The cancer cells then travel in the bloodstream to reach tissues and organs such as bones and liver, where they coat themselves with new proteins and start growing as metastases.  Dr. Overall has discovered that proteases secreted by cancer cells also disturb the way in which the nearby normal tissue, called stroma, and white blood cells protect the body against cancer.  He is using a new technique called proteomics to scan all the different proteins that metastases can produce, and to identify the proteins degraded by the proteases secreted by cancer cells.  One of these proteins degraded by metastases, called MCP3, relays messages between cells.  When MCP3 is degraded, it alters the signals that tell the immune system to fight cancer.  Dr. Overall's hypothesis is that this is one of the reasons why metastases are not detected by the immune system.  The team will also investigate the ways that cancers use proteases to become malignant.  They will design new anticancer drugs that target the proteases secreted by cancer cells.  These new drugs will also be used to visualize tumors inside a living body by PET (Positron Emission Tomography) scan, and help surgeons determine whether the tumors have spread, where to operate, and how effective treatments have been.

Dr. Calvin Roskelley - Cell Biology & Physiology, Dept. of Anatomy, UBC, Vancouver, B.C.

3-Dimensional culture modeling of metastatic breast cancer progression

Metastasis is the process by which tumor cells migrate away from the original tumor to different organs in the body, where they spread cancer.  This metastatic progression is the primary cause of death in breast cancer patients, and needs to be more fully understood.  Because it is difficult to carry out research on metastasis in humans, Dr. Roskelley proposes to design new models of cancer cells grown in the laboratory, which will closely mimic the tissue environment in the human breast and in the organs where breast cancer spreads.  In this project, the team will build microscopic breast, bone and liver tissues in culture dishes and use these tissues to test the function of genes thought to play a key role in metastasis.  This type of approach has been shown to generate clinically relevant results, which is not always the case when generic tissue culture systems are used.  In addition, the team will use these new models to screen for new compounds that are capable of inhibiting metastatic spread.  The results of this project should lead to a better understanding of the metastatic process at the gene level, and potentially to the development of non-toxic therapies against metastatic breast cancer.  

Dr. Arun Seth - Molecular & Cellular Biology Research, Sunnybrook & Women's College Health Sciences Centre, Toronto, ON

Metastatic breast cancer genome anatomy

To distinguish malignant breast tumors with the potential to spread to bones from those without this potential, it is necessary to have an experimental model to study tumor growth and invasion patterns.  To achieve this goal, Dr. Seth had developed a method of implanting human bone in laboratory mice, and his preliminary studies have shown that 40 per cent of primary breast tumors grew when placed into these human bone implants.  Dr. Seth proposes to use this model, which can distinguish between primary breast tumors with or without metastatic potential, to identify genes expressed at different levels in these two types of tumors.  The results of this research should provide in-depth information on breast cancer metastasis to bones and the genes implicated in this process.

For more information, please contact:
Nicole Adams
BC Cancer Agency
Tel: 604.877.6272
Pager: 604.641.5167
Email: nadams@bccancer.bc.ca