Ann Chambers, PhD

Ann Chambers

 

Distinguished Oncology Scientist: London Regional Cancer Program, London Health Sciences Centre, London, Ontario


Director: Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit


Canada Research Chair in Oncology: Canada Research Chairs


Professor of Oncology: University of Western Ontario, London, Ontario

Cross Appointments: Medical Biophysics and Pathology and Laboratory Medicine

 

Mailing Address

London Regional Cancer Program
Room A4-903b
Cancer Research Laboratory Program
790 Commissioners Rd. E.
London, Ontario
Canada N6A 4L6

Tel:  519.685.8652
Fax: 519.685.8646
Email: ann.chambers@lhsc.on.ca

Research Area


Biology and regulation of metastasis, tumor progression and dormancy

Summary of Current Work

Metastasis, Dormancy and Late Recurrence:  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 mechanisms that regulate metastasis and tumor dormancy. We learned that large numbers of dormant single cells may remain in secondary organs, with the potential to resume growth at later times to form metastases. These cells are resistant to cytotoxic chemotherapies that target dividing cells. We are working identifying vulnerabilities in dormant cells and new ways to target them therapeutically. We are using in vitro models to study the molecular regulation of tumor dormancy.  We are collaborating with Drs. Paula Foster and John Ronald to use novel cellular magnetic resonance and molecular imaging approaches to study metastasis and tumor dormancy.  In collaboration with Dr. Jim Lacefield, we are using small animal ultrasound approaches to quantify and model tumor growth and blood flow parameters. We are collaborating with Dr. Eugene Wong to develop new microfluidic devices to study interactions between cancer cells and their tissue microenvironment.

 

Osteopontin as a Biomarker and Regulator of Cancer Aggressiveness:  We are studying how an oncogene-induced, integrin-binding protein called osteopontin (OPN) contributes to the growth and progression of breast and other tumors, in collaboration with Dr. Alan Tuck.  We showed that OPN promotes malignancy of cells in culture, and we are studying how OPN affects tumor growth, progression and responses to targeted therapies. We developed an ELISA to measure OPN plasma levels in patients and in clinical studies, we learned that women with metastatic breast cancer, as well as men with castrate resistant prostate cancer, have elevated blood OPN levels.  OPN tissue levels are also elevated in tumor types. We found that elevated OPN levels in blood or tumor tissue 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 and predictive biomarker in breast, prostate and other cancers.

 

Early Breast Cancer Progression:  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. These biomarkers may help in determining the potential aggressiveness of early breast lesions, and refine treatment strategies for these patients.

 

The overall aim of our research is to learn how cancer cells spread, how they can become dormant and what triggers their awakening, in order that new approaches to prevent, delay or treat metastatic disease and late recurrences can be developed.

 

Publications


See my Publications on PubMed

See my Google Scholar Profile

Key Contributions

Brackstone M, Palma D, Tuck AB, Scott L, Potvin K, Vandenberg T, Perera F, D'Souza D, Taves D, Kornecki A, Muscedere G, Chambers AF.  2017.  Concurrent neoadjuvant chemotherapy and radiation therapy in locally advanced breast cancer. International Journal of Radiation Oncology Biology Physics doi.org/10.1016/j.ijrobp.2017.06.005 View Publication (PDF)V

Kirstein JM, Hague MN, McGowan PM, Tuck AB, Chambers AF. 2016. Primary melanoma tumor inhibits metastasis through alterations in systemic hemostasis. Journal of Molecular Medicine 94:899-910. View Publication (PDF) V

Barkan D, Chambers AF. 2016. Prevention of conversion of tumor dormancy into proliferative metastases. In: Cote R, Datar R (editors), Circulating Tumor Cells, Springer. Chapter 7, pp 121-137.View Publication (PDF)

Allan AL, Chambers AF. 2016. Circulating tumor cells and tumor dormancy. In: Cote R, Datar R (editors), Circulating Tumor Cells, Springer. Chapter 6, pp 101-120. View Publication (PDF) 

Chambers AF, Werb Z. 2015. Invasion and metastasis – Recent advances and future challenges, Journal of Molecular Medicine 93:361-368. View Publication (PDF)

Zarghami N, Jensen MD, Talluri S, Foster PJ, Chambers AF, Dick FA, Wong E. 2015. Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device. Medical Physics 42:6507-13.  doi: 10.1118/1.4933200. View Publication (PDF)

Bramwell VH, Tuck AB, Chapman JA, Anborgh PH, Postenka CO, Al-Katib W, Shepherd LE, Han L, Wilson CF, Pritchard KI, Pollak MN, Chambers AF. Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res. 2014 Jan 22;16(1):R8. doi: 10.1186/bcr3600. View Publication (PDF)

Barkan D, Chambers AF. 2011. β1-integrin: A potential therapeutic target in the battle against cancer recurrence.  Clinical Cancer Research 17:7219-23.

View Publication (PDF)

Goss PE, Chambers AF. 2010. Does tumour dormancy offer a therapeutic target? Nature Reviews Cancer 10: 871-877, 2010.

View Publication (PDF)

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.

View Publication (PDF)

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.

View Publication (PDF)

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.

View Publication (PDF)

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. 

View Publication (PDF)

Rittling SR, Chambers AF. 2004. Role of osteopontin in tumor progression.  British Journal of Cancer 90: 1877-1881.

View Publication (PDF)

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.

View Publication (PDF)

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.

View Publication (PDF)

Chambers AF, AC Groom and IC MacDonald. 2002. Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer 2: 563-572, 2002.

View Publication (PDF)

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.

View Publication (PDF)

Chambers AF, Matrisian LM. 1997. Changing views of the role of matrix metalloproteinases in metastasis.  Journal of the National Cancer Institute 89: 1260-1270.

View Publication (PDF)

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. 

View Publication (PDF)

David Holzman. 1996. New view of metastasis is spreading.  Journal of the National Cancer Institute 88:1336-1338.

View Publication (PDF)

Jocelyn Rice. Metastasis: The rude awakening.  Nature 485, S55–S57 (31 May 2012)

View Publication PDF

 

Key Collaborators

Alan B. Tuck, MD, PhD, FRCPC (Anatomic Pathology)

https://www.schulich.uwo.ca/pathol/people/bios/faculty/tuck_alan.html

Departments of Pathology and Oncology, University of Western Ontario

Staff Pathologist: Department of Pathology

Paula Foster http://www.robarts.ca/paula-foster

Robarts Research Institute, University of Western Ontario

 

John Ronald http://www.robarts.ca/john-ronald

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

Eugene Wong http://www.physics.uwo.ca/~ewong

Department of Physics and Astronomy, University of Western Ontario

 

Staff and Research Trainees

Research Associate:

Pieter Anborgh, PhD
Project: Experimental and clinical studies on the role of osteopontin in cancer
Email: Dr. Pieter Anborgh

 

Graduate Students:

Milica Krstic

PhD student, Pathology and Laboratory Medicine Department

Supervisor: Dr. Alan Tuck

Joint Supervisor: Dr. Ann Chambers

Project: Role of the transcriptional regulator TBX3 in early breast cancer progression

Email: Milica Krstic

David Uren

MSc student, Physics and Astronomy Department

Supervisor: Dr. Eugene Wong

Joint Supervisor: Dr. Ann Chambers  

Project: Design, fabrication and evaluation of microfluidic devices for the study of breast cancer metastasis

Email: David Uren

 

Research Technicians:

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)

 

 

 

 

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