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Distinguished Oncology Scientist: London Regional Cancer Program, London Health Sciences Centre, London, Ontario
Canada Research Chair in Oncology: Canada Research Chairs
Professor of Oncology: University of Western Ontario, London, Ontario
London Regional Cancer Program
Cancer Research Laboratory Program
790 Commissioners Rd. E.
Canada N6A 4L6
Cell and molecular biology of metastasis
Metastasis, the spread of cancer cells from a primary tumor to new sites, is a major factor in preventing successful treatment of cancer. Metastasis can occur after years of dormancy following treatment of a primary cancer. We are using experimental and clinical approaches to study metastasis and tumor dormancy. We have used in vivo videomicroscopy to clarify the steps and molecular mechanisms in metastasis. We have discovered that large numbers of dormant single cells may remain in secondary organs, with the potential to resume growth at later times to form metastases. We also are using in vitro models to study the molecular regulation of tumor dormancy. Our research suggests that new anti-metastatic therapies should be directed against the site-specific growth of cancer cells after they have arrived in the new organ. We are collaborating with Dr. Paula Foster to use novel cellular magnetic resonance imaging approaches to study metastasis and tumor dormancy. We also are collaborating with Dr. Jim Lacefield in the use of small animal ultrasound approaches to quantify and model tumor growth and blood flow parameters.
We also are studying how an oncogene-induced, integrin-binding protein called osteopontin (OPN) contributes to the growth and progression of many kinds of tumors, in collaboration with Dr. Alan Tuck, and spearheaded in the lab by Dr. Pieter Anborgh. We have shown that OPN can function to promote malignancy of cells in culture, and we are studying how OPN affects tumor growth and progression. We have developed an ELISA that can measure OPN plasma levels in patients. In clinical studies, we have shown that women with metastatic breast cancer, as well as men with castrate resistant prostate cancer, have blood OPN levels that are higher than normal levels, and that OPN tissue levels are higher in many types of tumors than in adjacent normal tissue. Elevated OPN levels are associated with poorer survival. These experimental and clinical studies will clarify the role of OPN functionally in cancer, and its potential role as a prognostic marker in breast, prostate and other cancers.
We recently have extended our biomarker studies to the analysis of circulating cancer microparticles, in blood from patients with various cancers. This work is being spearheaded by Dr. Hon Leong in the lab, in collaboration with clinical colleagues.
In collaboration with Dr. Tuck, we also are studying molecular determinants of early breast cancer progression. Using in vitro and in vivo models, we have identified a series of genes whose expression changes as breast cells progress from atypical ductal hyperplasia, to ductal carcinoma in situ, to invasive mammary carcinoma.
The overall aim of our research is to learn how cancer cells spread, in order that new approaches to prevent, delay or treat development of metastatic disease can be developed.
Barkan D, Chambers AF. 2011. β1-integrin: A potential therapeutic target in the battle against cancer recurrence. Clinical Cancer Research 17:7219-23.
Goss PE, Chambers AF. 2010. Does tumour dormancy offer a therapeutic target? Nature Reviews Cancer 10: 871-877, 2010.
Chambers AF. 2009. MDA-MB-435 and M14 cell lines: identical but not M14 melanoma? Cancer Research 69: 5292-5293.
Townson JL, Ramadan SS, Simedrea C, Rutt BK, MacDonald IC, Foster PJ, Chambers AF. 2009. Three-dimensional imaging and quantification of both solitary cells and metastases in whole mouse liver by magnetic resonance imaging. Cancer Research 69: 8326-8331.
Anborgh PH, Wilson SM, Tuck AB, Winquist E, Schmidt N, Hart R, Maeda M, Kon S, Uede T, Stitt LW, Chambers AF. 2009. New dual monoclonal ELISA for measuring plasma osteopontin as a biomarker associated with survival in prostate cancer: clinical validation and comparison of multiple ELISAs. Clinical Chemistry 55: 895-903.
Heyn C, Ronald JA, MacKenzie LT, MacDonald IC, Chambers AF, Rutt BK, Foster PJ. 2006. In vivo magnetic resonance imaging of single cells in mouse brain with optical validation. Magnetic Resonance in Medicine 55: 23-29.
Bramwell VHC, Doig GS, Tuck AB, Wilson SM, Tonkin KS, Tomiak A, Perera F, Vandenberg TA, Chambers AF. 2006. Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clinical Cancer Research 12: 3337-3343.
Graham KC, Wirtzfeld LA, MacKenzie LT, Postenka CO, Groom AC, MacDonald IC, Fenster A, Lacefield JD, Chambers AF. 2005. Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in pre-clinical models. Cancer Research 65: 5231-5237.
Rittling SR, Chambers AF. 2004. Role of osteopontin in tumor progression. British Journal of Cancer 90: 1877-1881.
Coppola D, Szabo M, Bouleware D, Muraca P, Alsarraj M, Chambers AF, Yeatman TJ. 2004. Correlation of OPN protein expression and pathologic stage across a wide variety of tumor histologies. Clinical Cancer Research 10: 184-190.
Naumov GN, Townson JL, MacDonald IC, Wilson SM, Bramwell VHC, Groom AC, Chambers AF. 2003. Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Research and Treatment 82: 199-206.
Chambers AF, AC Groom and IC MacDonald. 2002. Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer 2: 563-572, 2002.
Naumov GN, MacDonald IC, Weinmeister PM, Kerkvliet N, Nadkarni KV, Wilson SM, Morris VL, Groom AC, Chambers AF. 2002. Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. Cancer Research 62: 2162-2168.
Chambers AF, Matrisian LM. 1997. Changing views of the role of matrix metalloproteinases in metastasis. Journal of the National Cancer Institute 89: 1260-1270.
Singhal H, Bautista DS, Tonkin KS, O’Malley FP, Tuck AB, Chambers AF, Harris JF. 1997. Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clinical Cancer Research 3: 605-611.
Jocelyn Rice. Metastasis: The rude awakening. Nature 485, S55–S57 (31 May 2012)
Dr. Tuck is a pathologist, specializing in breast pathology, whose clinical work is based at London Health Sciences Center and St. Joseph's Health Centre, also affiliated with the London Regional Cancer Program. He is a consultant in breast pathology for SW Ontario. Research interests include the cell and molecular biology of breast cancer, osteopontin, tumor metastasis, and early development of models for studying breast cancer progression. This research is translational in nature, with the goal of developing new tools/targets for the management of patients at different stages of breast cancer.
Paula Foster http://www.robarts.ca/paula-foster
Robarts Research Institute, University of Western Ontario
James Lacefield http://www.eng.uwo.ca/people/jlacefield/Department of Electrical and Computer Engineering, University of Western Ont
Pieter Anborgh, PhD
Project: Experimental and clinical studies on the role of osteopontin in cancer
Email: Dr. Pieter Anborgh
Hon Sing Leong, PhD
Project: Novel imaging approaches, molecular regulation of metastasis and circulating cancer microparticles as biomarkers
Email: Dr. Hon Sing Leong
MSc student, Medical Biophysics Department
Supervisor: Dr. Jim Lacefield
Co-supervisor: Dr. Ann Chambers
Project: Power Doppler ultrasound and angiogenesis
Email: Matthew Lowerison
Muriel Brackstone, MD
PhD student, Pathology (part-time)
Project: Concurrent neoadjuvant chemo/radiation for locally advanced breast cancer – understanding and predicting treatment resistance
Email: Dr. Muriel Brackstone
MSc student, Pathology
Supervisor: Dr. Alan Tuck
Co-supervisor: Dr. Ann Chambers
Project: Role of the transcriptional regulator TBX3 in early breast cancer progression
Email: Milica Krstic
David Dales, BSc (Honours Genetics), Senior Research Technician
Specialty: Molecular and cellular biology and overall laboratory management
Email David Dales
Nicole Hague, BSc, RVT
Specialty: Veterinary technician
Email Nicole Hague
Carl Postenka, BSc, M.L.T., Histology Research Technician
Specialty: Animal handling and all aspects of histology (with Dr. Alan Tuck)
Email Carl Postenka
Joseph Andrews, Bsc, MSc, Research Technician
Specialty: Microarray technology, molecular biology;
bioinformatics (with Dr. David Rodenhiser)
Email Joseph Andrews
Colleen Biggs, BSc, Research Technician
Specialty: Microparticle analyses
Email: Colleen Biggs
Siddika Pardhan, BSc, Research Technician
Specialty: Molecular biology and in vivo assays
Email: Siddika Pardhan
Chantalle Willie, BSc, Research Technician
Specialty: Cell culture and clinical sample coordination
Email: Chantalle Willie