NRC Award Recipient Contributing in Fight Against Breast Cancer

		H.L. Holmes Award for Post-Doctoral Studies
		The next round of competitions will begin in mid-October 2005.
		The deadline for applications will be January 31, 2005 with a view to begin funding by the Spring of 2005.
		For more information on the H.L. Holmes Award and how to apply.

Since May 2003, Dr. Alison Allan, supported by a special award from National Research Council, has been working diligently in the fight against breast cancer. Dr. Allan, the 2003-04 recipient of the H.L. Holmes Award for Post-Doctoral Studies received over $180K to fund research that examines an important prognostic indicator and potential therapeutic target in breast cancer patients.

Dr. Allan holds a Ph.D. in Biomedical Sciences from the University of Guelph, where she also completed her undergraduate studies in molecular biology and genetics. She is conducting her research in the laboratory of Dr. Ann Chambers and Dr. Alan Tuck through the London Regional Cancer Program at the London Health Sciences Centre in London, Ontario. This facility houses the Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, and is also closely affiliated with the Department of Oncology at the University of Western Ontario.

Osteopontin could provide clues in breast cancer and metastasis

Dr. Alison Allan

Dr. Allan set out to examine the functional role of the protein, Osteopontin (OPN), in breast cancer and metastasis - the spread of cancer cells from a primary site and the establishment of secondary tumors in distant locations. OPN is a secreted phosphoprotein that has been found to play a role in certain medical conditions, including cancer.

The scientific rationale behind Dr. Allan's project is correlated to current studies undertaken through the London Regional Cancer Program which have shown that the protein OPN is highly expressed in the blood and tumor tissue of breast cancer patients, and that OPN expression levels can be positively correlated with increased metastatic disease, poor prognosis, and decreased survival.

Hypothetically, the over-expression of OPN in breast cancer could be due to one of two situations:

1. increased levels of OPN could be a consequence of the cancer, meaning that some biological activity caused by the disease situation could be increasing OPN expression; or
2. increased levels of OPN could be a contributing cause of the cancer, meaning that increased expression of OPN in normal breast cells could be causing them to make cells become more malignant and/or metastatic.

Possible mechanisms for the over-expression of OPN in breast cancer metastasis. Understanding the molecular mechanisms of action of OPN in breast cancer cells, particularly with regards to its interaction with integrins, which have also been implicated as contributors to cancer progression. Gaining this understanding will be important in order to determine, for future studies, if OPN (and/or the interaction between OPN and integrins) is suitable as a new therapeutic target to combat breast cancer.

Dr. Allan and her colleagues suspect that the latter situation is the case and that OPN is functionally contributing toward making breast cancer cells more metastatic. However, the molecular mechanisms by which OPN might do this remain poorly understood.

The overall goal of the project is to understand the molecular mechanisms of action of OPN in breast cancer cells, particularly with regards to its interaction with another family of proteins called, integrins, which have also been implicated as contributors to cancer progression. Gaining this understanding will be important in order to determine, for future studies, if OPN (and/or the interaction between OPN and integrins) is suitable as a new therapeutic target to combat breast cancer.

Major milestones

The first step in undertaking this project was to develop and characterize an experimental model system with which to study OPN. Dr. Allan and her team have developed such a model and are using it to determine if over-expression of OPN can increase the malignant/metastatic behavior of human breast cancer cells.

Preliminary results indicate that over-expression of OPN can indeed promote increased malignant behavior (such as cellular adhesion, migration, and invasion) in vitro, and promote the development of metastatic lesions in vivo in regional organ sites such as lymph nodes and in distant organ sites such as lungs. These findings are exciting and important because the ability of OPN to functionally contribute to human breast cancer metastasis had not previously been demonstrated.

One year into her two-year term with NRC Holmes Award funding, Dr. Allan's research is progressing well. She is continuing in her attempt to determine if this OPN-mediated malignancy and metastasis is reliant on its ability to interact with integrins.

Publications and Speaking Opportunities

While carrying out the research project over the past year, Dr. Allan has written and published one research paper, two book chapters, and three abstracts relating to OPN and metastasis.

In March of this year, she presented her research at the international conference of the American Association of Cancer Research in Orlando, Florida. She has recently been invited to speak about her findings at the Alberta Cancer Board Annual Meeting to be held in Banff in November of 2004.

NRC Holmes Award

When asked how NRC's Holmes Award has impacted her research career, Dr. Allan states that, "the opportunity to work with Dr. Ann Chambers, an internationally recognized leader in metastasis research, continues to be a tremendously rewarding experience, both in terms of personal and professional development."

One of the objectives of the Holmes Award is to enhance Canadian research through post-doctoral studies under outstanding research persons at world-renowned graduate schools or research institutes. Our award recipient has benefited on this front and explains that, "being situated at a world-class facility such as the London Regional Cancer Program at the London Health Sciences Centre has provided the perfect environment for my continued development as a young scientific investigator in Canada."

The H.L. Holmes Award has been established by the National Research Council Canada (NRC) in honour of the late Dr. R.H.L. Holmes, a chemist who spent most of his research career in Alberta.

Awards cover a one or two-year period, depending on available funding and the research proposal, and can have a monetary value of up to $100,000 per year. Research must be undertaken in the fields of chemistry, physics, biology and mathematics related to medical and biological processes.

NRC employees are eligible for the H.L. Holmes Award, provided they meet the selection criteria.

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