Alison L. Allan, PhD

Alison Allan, PhD

Oncology Scientist, London Regional Cancer Program, London Health Sciences Centre

Cross-Appointments: Assistant Professor, Departments of Oncology and Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario

Mailing Address:

Cancer Research Laboratory Program
London Regional Cancer Program, London Health Sciences Centre
Victoria Research Labs, Room A4-132
London, Ontario
Canada N6A 4L6

Tel: 519.685.8600 Ext. 55134
Fax: 519.685.8616
Email: alison.allan@lhsc.on.ca

University website: http://www.uwo.ca/anatomy/department/allana/aallan.html

Research Area

Cellular and molecular biology of metastasis

Key Words: Breast cancer, prostate cancer, metastasis, circulating tumor cells, cancer stem cells, osteopontin, translational research

Staff and Trainees

Ying Xia, Postdoctoral Research Associate

Project: Single Cell analysis of heterogeneous circulating tumor cells and cancer stem cells

Email: ying.xia@lhsc.on.ca

David Goodale, Research Technician

Project: Detection and analysis of circulating tumor cells in mouse models of breast cancer
Email: david.goodale@lhsc.on.ca

Alysha Croker, PhD Graduate Student (Dept. of Anatomy & Cell Biology)

Project: Role cancer stem cells in breast cancer metastasis and treatment
Email: acroker@uwo.ca

Lori Lowes, M.Sc. Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Molecular characterization of circulating tumor cells in breast and prostate cancer
Email: llowes@uwo.ca

Irene Ma, M.Sc. Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Functional role of aldehyde dehydrogenase (ALDH) and CD44 in breast cancer metastasis
Email: ima@uwo.ca

Jenny Chu, M.Sc. Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Organ tropism of stem-like breast cancer cells
Email: jchu87@uwo.ca

Research Interests:

Dr. Allan's research interests lie in the study of molecular mechanisms that influence normal cellular growth, tumor development, and cancer progression. The focus of Dr. Allan's research program is breast cancer metastasis and translational research. Despite the fact that the majority of deaths from solid cancer occur due to the physiological effects of metastasis rather than from the consequences of the primary tumor, metastasis remains a badly understudied field. A major area of research that is needed to address this problem involves gaining a greater understanding of the metastatic process as a whole, such that current therapies can be better utilized to target metastatic disease, and new, more effective therapies can be developed which will better treat or prevent cancer metastasis. A second important area of research is the identification and development of surrogate marker approaches that will allow close monitoring of both disease progression and response to therapy. Dr. Allan's research program encompasses both of these areas, and involves three individual but interrelated projects in the areas of metastasis, cancer stem cells, tumor biology, and molecular oncology.

Current Projects:

1. Detection and analysis of circulating tumor cells in cancer patients and mouse models of breast cancer:
Clinical studies have shown that rare disseminated tumor cells in the peripheral bloodstream or bone marrow of patients with breast and other cancers may be an important indicator of the potential for metastatic disease and poor prognosis. However, the biological implications of these cells remain poorly understood, particularly with regards to the functional and mechanistic details of their progression to clinically relevant metastases. Our lab has established novel and sensitive methods to identify and characterize rare disseminated tumor cells in the blood, bone marrow, and distant organ sites in mouse models of human breast cancer, as well as in the peripheral blood of cancer patients. These studies are helping us elucidate the mechanistic details of early steps in metastasis and how these steps relate to the development of life-threatening metastases in animal models and patients. In addition, these methods will be extremely valuable for the future identification, development, and testing of new therapeutic strategies to combat breast and other cancers.

Recent Publications in this Area

Lowes LE, Goodale D, Keeney M, Allan AL. Image cytometry analysis of circulating tumor cells. Methods Cell Biol. 2011;102:261-90.

Allan A.L., and Keeney M. Circulating tumor cell (CTC) analysis: technical and statistical considerations for application to the clinic. J Oncol. 2010; 2010:426218. Epub 2009 Dec 13.

Goodale, D., Phay, C., Postenka, C., Keeney, M., and Allan A.L. Characterization of tumor cell dissemination patterns in preclinical models of breast cancer metastasis using flow cytometry and laser scanning cytometry. Cytometry A. 2009, 75(4):344-55.

Goodale, D., Phay, C., Brown, W., Gray-Statchuk, L., Furlong, P., Lock, M., Chin-Yee, I., Keeney, M., and Allan, A.L. Flow cytometric assessment of monocyte activation markers and circulating endothelial cells in patients with localized or metastatic breast cancer. Cytometry B Clin Cytom. 2009, 76B (2):107-117.

2. Role of cancer stem cells in breast cancer metastasis and treatment:
Metastasis is an inefficient process, such that very few cells that leave a tumor successfully form macrometastases in distant sites. This, coupled with the inherently heterogeneous nature of the cancer cell population within solid tumors, suggests that only a small subpopulation of cells can successfully initiate tumor growth and navigate the metastatic cascade to eventually form life-threatening metastases in distant organs. We hypothesize that this rare subpopulation of cells are in fact cancer stem cells (CSCs). Recent experimental studies in our lab indicate that breast cancer cells with a "stem-like" phenotype display enhanced adhesion, migration, invasion, and metastasis. In collaboration with the LHSC Divisions of Surgery, Oncology, and Hematology, our lab has also undertaken translational studies aimed at characterizing breast cancer CSCs in patient samples, including assessment of the role that CSCs play in patient response to chemotherapy and radiation treatment. Taken together, these novel studies will allow us to answer a number of important and previously uninvestigated questions regarding the role of CSCs in breast cancer metastasis and treatment. Although some early stage cancers can be successfully treated by surgery, radiation, and/or chemotherapy, the majority of current therapies fail in the metastatic setting. Therefore, our consideration of the CSC hypothesis in the context of metastasis and response to therapy could have far-reaching implications to the way that we not only study cancer, but more importantly how we treat it.

Recent Publications in this Area

Hess DA, Allan AL. Migratory Strategies of Normal and Malignant Stem Cells. Methods Mol Biol. 2011;750:25-44.

Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. 2011 Jun;7(2):292-306.

Croker, A.K., Goodale, D., Chu, J., Postenka, C., Hedley, B.D., Hess, D.A., and Allan, A.L. High aldehyde dehydrogenase activity and expression of cancer stem cell markers selects for stem-like breast cancer cells with enhanced malignant and metastatic properties. J Cell Mol Med. 2009, 13(8b), 2236-2252.

Goss, P., Allan, A.L., Rodenhiser, D.I., Foster, P.J., and Chambers, A.F. New clinical and experimental approaches for studying tumor dormancy: does tumor dormancy offer a therapeutic target? APMIS 116: 552-568, 2008.

Croker, A.K., and Allan, A.L. Cancer stem cells: implications for progression and treatment of metastatic disease. J. Cell. Mol. Med. 2008 Mar-Apr;12(2):374-90.

3. Interaction of osteopontin and integrins during breast cancer metastasis:
Osteopontin (OPN) is a secreted integrin-binding protein that has been shown to be associated with breast and other cancers. Clinical studies have shown that increased OPN levels in breast cancer patients can be correlated with increased tumor aggressiveness and poor prognosis. However, the mechanisms by which this occurs required further characterization. Our previous work has shown that OPN is key molecular player involved in lymphatic metastasis of breast cancer, potentially by affecting integrin-mediated adhesive interactions between tumor cells and their microenvironment. Ongoing work in the lab is investigating how microenvironmental factors such as thrombin may also contribute to OPN-mediated malignancy, and the role of integrin signaling in this process.

Recent Publications in this Area

Beausoleil MS, Schulze EB, Goodale D, Postenka CO, Allan AL. Deletion of the thrombin cleavage domain of osteopontin mediates breast cancer cell adhesion, proteolytic activity, tumorgenicity, and metastasis. BMC Cancer. 2011 Jan 19;11:25.

Schulze, E.B., Hedley, B.D., Goodale, D., Postenka, C.O., Al-Katib, W., Tuck, A.B., Chambers, A.F., and Allan, A.L. The thrombin inhibitor Argatroban reduces osteopontin-mediated breast cancer malignancy and metastasis. Breast Cancer Res. Treat. 2008, 112(2):243-54.

Hedley, B.D., Welch, D.R, Allan, A.L., Al-Katib,W., Dales, D.W., Postenka, C.O., MacDonald , I.C., and Chambers, A.F. Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1. Int. J. Cancer. 2008, 123(3):526-34.

Key Collaborators:

Michael Keeney, ART, FIMLS
Hematology/Flow Cytometry, London Health Sciences Centre; and Lawson Health Research Institute

David Hess, Ph.D.
Stem Cell Biology, Robarts Research Institute

Anargyros Xenocostas, MD, FRCPC
Hematology, London Health Sciences Centre; and Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario

Tracy Sexton, MD, PhD, FRCPC
Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre; and Departments of Oncology and Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario

Michael Lock, MD, CCFP, FRCPC
Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre; and Department of Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario

Muriel Brackstone, MSc, MD, FRCPC
Surgical Oncology, London Regional Cancer Program, London Health Sciences Centre; and Departments of Surgery and Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario

Ann F. Chambers, Ph.D.
Cancer Research, London Regional Cancer Program, London Health Sciences Centre; and Departments of Oncology, Medical Biophysics, Pathology, and Microbiology & Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario

Jeremy Squire, Ph.D.

Department of Pathology and Molecular Medicine, Kingston General Hospital and Queen’s University; and National Cancer Institute of Canada Clinical Trials Group