University of Western Ontario Schulich School of Medicine & Dentistry Oncology Associate ProfessorAppointed: 1988 | |
QualificationsPh.D., Duke University, Zoology, 1978. B.A., Duke University, Botany, 1973. Expertise and Research InterestsThe research focus of my laboratory is the molecular genetics and cell biology of tumor progression and metastasis. One of two major areas of current study is the role of the ras oncogene in tumor metastasis (the spread of cancer). We were among the firstto report, in 1985, that an activated ras oncogene could contribute to metastatic ability, when we showed that NIH 3T3 cells transfected with the H-ras oncogene became metastatic. We have since demonstrated a quantitative relationship between levels of ras encoded p21 protein and metastatic ability in these cells, using metastasis assays in both nude mice and in a novel assay we developed using chick embryos.
We hypothesize that the ras oncogene induces expression of a variety of other genes, some of which are involved in metastatic behavior of the cells. We are now examining genes induced by ras, including one coding for a secreted phosphoprotein (sppl) thatmay have cell adhesive function, in studies directed at identifying mechanisms by which ras may induce increases in metastatic ability. We are studying these ras-induced genes, both for their possible contribution to metastatic ability and for mechanismsby which the ras oncogene can regulate gene expression. We have transfected ras transformed, metastatic cells with plasmids containing antisense complementary deoxyribonucleic acid (cDNA) for the sppl gene and have obtained apparently down regulated clones. We are in the process of characterizing the effects (on metastasis and cell adhesion) of down regulation of sppl in these cells. In addition, we are examining promoter elements upstream of the sppl gene, to identify ras responsive elements that may control sppl gene expression. We are also studying ras-induced changes in expression of genes encoding proteinases and their inhibitors in these cells.
In related work, we are studying a cell line, LTA, which is apparently resistant to the ras oncogene. LTA cells are tumorigenic but nonmetastatic. They remain nonmetastatic following transfection and expression of a ras oncogene, as well as ras plus myc oncogenes. We are studying possible mechanisms of oncogene resistance in these cells. These studies may help us to learn about natural mechanisms by which cells can resist alterations induced by oncogenes.
In collaborative studies with Dr J F Harris, we are studying somatic cell genetic properties of metastatic tumor cells. Recently, we documented that ras transformed cells are not uniformly more resistant to radiation, in a study that countered reports that this might be so. Our finding has clinical relevance, in that ras induced radioresistance, had it been a uniform finding, would have affected treatment of tumors carrying activated ras oncogenes. In addition, we are examining factors secreted by tumor cells that may alter the development of heterogeneity during growth of tumor cell clones.
Other ExpertiseExperimental models for tumor metastasis.
Tumor heterogeneity.
Molecular biology of tumor progression and metastasis. KeywordsCOS Keywords:Gene Expression, Medical Disciplines or Fields, Metastasis, Molecular Genetics, Oncology, Signal Transduction, Specialties of Medical and Allied Fields.Additional Terms:Chick Embryo, Clonal Heterogeneity, Gene Expression, Metastasis, Oncogene, Oncology, Osteopontin, Radiation Molecular Genetics, Ras, Signal Transduction, Tumor Cell, Tumor Progression.Languages(Reading, Writing, Speaking)French: (Basic, Basic, Basic) French: (Basic, Basic, Basic) MembershipsAmerican Association for Cancer Research American Association for the Advancement of Science American Society for Cell Biology Canadian Society for Cell Biology Metastasis Research Society Previous Positions1979-1982, Ontario Cancer Institute, Postdoctoral Fellow 1982- 1983, Ontario Cancer Institute, Research Associate 1983-1988, University of Western Ontario, Assistant Professor 1983-Present, London Regional Cancer Center, Career Scientist Publications- Nutt CL, Loktionova NA, Pegg AE, Chambers AF, Cairncross JG, O(6\)-methylguanine-DNA methyltransferase activity, p53 gene status and BCNU resistance in mouse astrocytes., Carcinogenesis, 20(12), 2361-5, December 1999
 - Groom AC, MacDonald IC, Schmidt EE, Morris VL, Chambers AF, Tumour metastasis to the liver, and the roles of proteinases and adhesion molecules: new concepts from in vivo videomicroscopy., Canadian Journal of Gastroenterology, 13(9), 733-43, November 1999
 - Tuck AB, Arsenault DM, O''Malley FP, Hota C, Ling MC, Wilson SM, Chambers AF, Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells., Oncogene, 18(29), 4237-46, 22 Jul 1999
 - Naumov GN, Wilson SM, MacDonald IC, Schmidt EE, Morris VL, Groom AC, Hoffman RM, Chambers AF, Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis., Journal of Cell Science, 112 \( Pt 12\), 1835-42, June 1999
 - Wylie S, MacDonald IC, Varghese HJ, Schmidt EE, Morris VL, Groom AC, Chambers AF, The matrix metalloproteinase inhibitor batimastat inhibits angiogenesis in liver metastases of B16F1 melanoma cells., Clinical and Experimental Metastasis, 17(2), 111-7, March 1999
 - Tuck A B, O'Malley F P, Singhal H, Harris J F, Tonkin K S, Kerkvliet N, Saad Z, Doig G S, Chambers A F, Osteopontin expression in a group of lymph node negative breast cancer patients., International Journal of Cancer, 79(5), 502-8, 23 Oct 1998
 - Luzzi K J, MacDonald I C, Schmidt E E, Kerkvliet N, Morris V L, Chambers A F, Groom A C, Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases., American Journal of Pathology, 153(3), 865-73, September 1998
 - Atkins K, Berry J E, Zhang W Z, Harris J F, Chambers A F, Simpson R U, Somerman M J, Coordinate expression of OPN and associated receptors during monocyte/macrophage differentiation of HL-60 cells., Journal of Cellular Physiology, 175(2), 229-37, May 1998
 - Saad Z, Bramwell V H, Wilson S M, O'Malley F P, Jeacock J, Chambers A F, Expression of genes that contribute to proliferative and metastatic ability in breast cancer resected during various menstrual phases., Lancet, 351(9110), 1170-3, 18 Apr 1998
 - Xuan J W, Tuck A B, Wilson S M, Chin J L, Chambers A F, MMP-2 expression is associated with, but not sufficient for, malignant conversion of murine LTA cells., Anticancer Research, 18(2A), 743-9, March 1998
 - Chambers AF, MacDonald IC, Schmidt EE, Morris VL, Groom AC, Preclinical assessment of anti-cancer therapeutic strategies using in vivo videomicroscopy., Cancer and Metastasis Reviews, 17(3), 263-9, 1998
 - Casson A G, Wilson S M, McCart J A, O'Malley F P, Ozcelik H, Tsao M S, Chambers A F, ras mutation and expression of the ras-regulated genes osteopontin and cathepsin L in human esophageal cancer., International Journal of Cancer, 72(5), 739-45, 4 Sep 1997
 - Chambers A F, Matrisian L M, Changing views of the role of matrix metalloproteinases in metastasis., Journal of The National Cancer Institute, 89(17), 1260-70, 3 Sep 1997
 - Tuck A B, O'Malley F P, Singhal H, Tonkin K S, Harris J F, Bautista D, Chambers A F, Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas., Archives of Pathology and Laboratory Medicine, 121(6), 578-84, June 1997
 - Singhal H, Bautista DS, Tonkin KS, O''Malley FP, Tuck AB, Chambers AF, Harris JF, Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival., Clinical Cancer Research, 3(4), 605-11, April 1997
 - Guthrie N, Gapor A, Chambers A F, Carroll K K, Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination., Journal of Nutrition, 127(3), 544S-548S, March 1997
 - So F V, Guthrie N, Chambers A F, Carroll K K, Inhibition of proliferation of estrogen receptor-positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess estrogen., Cancer Letters, 112(2), 127-33, 30 Jan 1997
 - Morris VL, Schmidt EE, MacDonald IC, Groom AC, Chambers AF, Sequential steps in hematogenous metastasis of cancer cells studied by in vivo videomicroscopy., Invasion and Metastasis, 17(6), 281-96, 1997
 - Chambers A F, Wilson S M, Kerkvliet N, O'Malley F P, Harris J F, Casson A G, Osteopontin expression in lung cancer., Lung Cancer, 15(3), 311-23, November 1996
 - Koop S, Schmidt E E, MacDonald I C, Morris V L, Khokha R, Grattan M, Leone J, Chambers A F, Groom A C, Independence of metastatic ability and extravasation: metastatic ras-transformed and control fibroblasts extravasate equally well., Proceedings of the National Academy of Sciences (USA), 93(20), 11080-4, 1 Oct 1996
 - Engel C J, Bennett S T, Chambers A F, Doig G S, Kerkvliet N, O'Malley F P, Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging., American Journal of Surgical Pathology, 20(10), 1260-5, October 1996
 - O'Malley F P, Saad Z, Kerkvliet N, Doig G, Stitt L, Ainsworth P, Hundal H, Chambers A F, Turnbull D I, Bramwell V, The predictive power of semiquantitative immunohistochemical assessment of p53 and c-erb B-2 in lymph node-negative breast cancer., Human Pathology, 27(9), 955-63, September 1996
 - Hahn F M, Xuan J W, Chambers A F, Poulter C D, Human isopentenyl diphosphate: dimethylallyl diphosphate isomerase: overproduction, purification, and characterization., Archives of Biochemistry and Biophysics, 332(1), 30-4, 1 Aug 1996
 - Hangan D, Uniyal S, Morris V L, MacDonald I C, von Ballestrem C, Chau T, Schmidt E E, Chambers A F, Groom A C, Chan B M, Integrin VLA-2 (alpha2beta1) function in postextravasation movement of human rhabdomyosarcoma RD cells in the liver., Cancer Research, 56(13), 3142-9, 1 Jul 1996
 - Nutt C L, Chambers A F, Cairncross J G, Wild-type p53 renders mouse astrocytes resistant to 1,3-Bis(2-chloroethyl)-1-nitrosourea despite the absent of a p53-dependent cell cycle arrest., Cancer Research, 56(12), 2748-51, 15 Jun 1996
 - Bautista D S, Denstedt J, Chambers A F, Harris J F, Low-molecular-weight variants of osteopontin generated by serine proteinases in urine of patients with kidney stones., Journal of Cellular Biochemistry, 61(3), 402-9, 1 Jun 1996
 - Bautista D S, Saad Z, Chambers A F, Tonkin K S, O'Malley F P, Singhal H, Tokmakejian S, Bramwell V, Harris J F, Quantification of osteopontin in human plasma with an ELISA: basal levels in pre- and postmenopausal women., Clinical Biochemistry, 29(3), 231-9, June 1996
 - So F V, Guthrie N, Chambers A F, Moussa M, Carroll K K, Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices., Nutrition and Cancer, 26(2), 167-81, 1996
 - Nesaretnam K, Guthrie N, Chambers A F, Carroll K K, Effect of tocotrienols on the growth of a human breast cancer cell line in culture., Lipids, 30(12), 1139-43, December 1995
 - Chambers A F, MacDonald I C, Schmidt E E, Koop S, Morris V L, Khokha R, Groom A C, Steps in tumor metastasis: new concepts from intravital videomicroscopy., Cancer and Metastasis Reviews, 14(4), 279-301, December 1995
 - Xuan J W, Chin J L, Guo Y, Chambers A F, Finkelman M A, Clarke M W, Alternative splicing of PSP94 (prostatic secretory protein of 94 amino acids) mRNA in prostate tissue., Oncogene, 11(6), 1041-7, 21 Sep 1995
 - Morris V L, Schmidt E E, Koop S, MacDonald I C, Grattan M, Khokha R, McLane M A, Niewiarowski S, Chambers A F, Groom A C, Effects of the disintegrin eristostatin on individual steps of hematogenous metastasis., Experimental Cell Research, 219(2), 571-8, August 1995
 - Xuan J W, Wilson S M, Chin J L, Chambers A F, Metastatic NIH 3T3 x LTA cell hybrids express 72 kDa type IV collagenase., Anticancer Research, 15(4), 1227-33, July 1995
 - Koop S, MacDonald I C, Luzzi K, Schmidt E E, Morris V L, Grattan M, Khokha R, Chambers A F, Groom A C, Fate of melanoma cells entering the microcirculation: over 80% survive and extravasate., Cancer Research, 55(12), 2520-3, 15 Jun 1995
 - Nutt C L, Costello J F, Bambrick L L, Yarosh D B, Swinnen L J, Chambers A F, Cairncross J G, O6-methylguanine-DNA methyltransferase in tumors and cells of the oligodendrocyte lineage., Canadian Journal of Neurological Sciences, 22(2), 111-5, May 1995
 - Bautista D S, Xuan J W, Hota C, Chambers A F, Harris J F, A monoclonal antibody against osteopontin inhibits RGD-mediated cell adhesion to osteopontin., Annals of The New York Academy of Sciences, 760, 309-11, 21 Apr 1995
 - Behrend E I, Craig A M, Wilson S M, Denhardt D T, Chambers A F, Expression of antisense osteopontin RNA in metastatic mouse fibroblasts is associated with reduced malignancy., Annals of The New York Academy of Sciences, 760, 299-301, 21 Apr 1995
 - Chambers A F, Regulation and function of osteopontin in ras-transformed cells., Annals of The New York Academy of Sciences, 760, 101-8, 21 Apr 1995
 - Xuan J W, Hota C, Shigeyama Y, D'Errico J A, Somerman M J, Chambers A F, Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functions., Journal of Cellular Biochemistry, 57(4), 680-90, April 1995
 - Guo X, Zhang Y P, Mitchell D A, Denhardt D T, Chambers A F, Identification of a ras-activated enhancer in the mouse osteopontin promoter and its interaction with a putative ETS-related transcription factor whose activity correlates with the metastatic potentia, Molecular and Cellular Biology, 15(1), 476-87, January 1995
 - Morris V L, Koop S, MacDonald I C, Schmidt E E, Grattan M, Percy D, Chambers A F, Groom A C, Mammary carcinoma cell lines of high and low metastatic potential differ not in extravasation but in subsequent migration and growth., Clinical and Experimental Metastasis, 12(6), 357-67, November 1994
 - Bautista D S, Xuan J W, Hota C, Chambers A F, Harris J F, Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin., Journal of Biological Chemistry, 269(37), 23280-5, 16 Sep 1994
 - Koop S, Khokha R, Schmidt E E, MacDonald I C, Morris V L, Chambers A F, Groom A C, Overexpression of metalloproteinase inhibitor in B16F10 cells does not affect extravasation but reduces tumor growth., Cancer Research, 54(17), 4791-7, 1 Sep 1994
 - Denhardt D T, Chambers A F, Overcoming obstacles to metastasis--defenses against host defenses: osteopontin (OPN) as a shield against attack by cytotoxic host cells., Journal of Cellular Biochemistry, 56(1), 48-51, September 1994
 - van Meyel D J, Ramsay D A, Casson A G, Keeney M, Chambers A F, Cairncross J G, p53 mutation, expression, and DNA ploidy in evolving gliomas: evidence for two pathways of progression., Journal of The National Cancer Institute, 86(13), 1011-7, 6 Jul 1994
 - Kothapalli R, Lui E M, Guthrie N, Chambers A F, Carroll K K, Effects of long-chain fatty amines on the growth of ras-transformed NIH 3T3 cells., Biochemical Pharmacology, 47(10), 1909-16, 18 May 1994
 - Xuan J W, Kowalski J, Chambers A F, Denhardt D T, A human promyelocyte mRNA transiently induced by TPA is homologous to yeast IPP isomerase., Genomics, 20(1), 129-31, 1 Mar 1994
 - Xuan J W, Hota C, Chambers A F, Recombinant GST-human osteopontin fusion protein is functional in RGD-dependent cell adhesion., Journal of Cellular Biochemistry, 54(2), 247-55, February 1994
 - Behrend E I, Craig A M, Wilson S M, Denhardt D T, Chambers A F, Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense osteopontin RNA., Cancer Research, 54(3), 832-7, 1 Feb 1994
 - Sorsdahl K, Casson A G, Troster M, Van Meyel D, Inculet R, Chambers A F, p53 and ras gene expression in human esophageal cancer and Barrett's epithelium: a prospective study., Cancer Detection and Prevention, 18(3), 179-85, 1994
 - van Meyel D J, Ramsay D A, Chambers A F, Macdonald D R, Cairncross J G, Absence of hereditary mutations in exons 5 through 9 of the p53 gene and exon 24 of the neurofibromin gene in families with glioma., Annals of Neurology, 35(1), 120-2, January 1994
 - Kothapalli R, Guthrie N, Chambers A F, Carroll K K, Farnesylamine: an inhibitor of farnesylation and growth of ras-transformed cells., Lipids, 28(11), 969-73, November 1993
 - Morris V L, MacDonald I C, Koop S, Schmidt E E, Chambers A F, Groom A C, Early interactions of cancer cells with the microvasculature in mouse liver and muscle during hematogenous metastasis: videomicroscopic analysis [see comments], Clinical and Experimental Metastasis, 11(5), 377-90, September 1993
 - Behrend E I, Chambers A F, Wilson S M, Denhardt D T, Comparative analysis of two alternative first exons reported for the mouse osteopontin gene., Journal of Biological Chemistry, 268(15), 11172-5, 25 May 1993
 - Chambers A F, Hota C, Prince C W, Adhesion of metastatic, ras-transformed NIH 3T3 cells to osteopontin, fibronectin, and laminin., Cancer Research, 53(3), 701-6, 1 Feb 1993
 - Morris V L, Tuck A B, Wilson S M, Percy D, Chambers A F, Tumor progression and metastasis in murine D2 hyperplastic alveolar nodule mammary tumor cell lines., Clinical and Experimental Metastasis, 11(1), 103-12, January 1993
 - Chambers A F, Tuck A B, Ras-responsive genes and tumor metastasis., Critical Reviews In Oncogenesis, 4(2), 95-114, 1993
 - Khokha R, Zimmer M J, Wilson S M, Chambers A F, Up-regulation of TIMP-1 expression in B16-F10 melanoma cells suppresses their metastatic ability in chick embryo., Clinical and Experimental Metastasis, 10(6), 365-70, November 1992
 - Chambers A F, Mechanisms of oncogene-mediated alterations in metastatic ability., Biochemistry and Cell Biology, 70(9), 817-21, September 1992
 - MacDonald I C, Schmidt E E, Morris V L, Chambers A F, Groom A C, Intravital videomicroscopy of the chorioallantoic microcirculation: a model system for studying metastasis., Microvascular Research, 44(2), 185-99, September 1992
 - Chambers A F, Schmidt E E, MacDonald I C, Morris V L, Groom A C, Early steps in hematogenous metastasis of B16F1 melanoma cells in chick embryos studied by high-resolution intravital videomicroscopy., Journal of The National Cancer Institute, 84(10), 797-803, 20 May 1992
 - Chambers A F, Colella R, Denhardt D T, Wilson S M, Increased expression of cathepsins L and B and decreased activity of their inhibitors in metastatic, ras-transformed NIH 3T3 cells., Molecular Carcinogenesis, 5(3), 238-45, 1992
 - Chambers A F, Behrend E I, Wilson S M, Denhardt D T, Induction of expression of osteopontin (OPN; secreted phosphoprotein) in metastatic, ras-transformed NIH 3T3 cells., Anticancer Research, 12(1), 43-7, January 1992
 - Chambers A F, Denhardt G H, Wilson S M, Cairncross J G, Malignant properties of P635 glioma are independent of glial fibrillary acidic protein expression., Journal of Neuro-oncology, 11(1), 43-8, August 1991
 - Tuck A B, Wilson S M, Sergovich F R, Chambers A F, Gene expression and metastasis of somatic cell hybrids between murine fibroblast cell lines of different malignant potential., Somatic Cell and Molecular Genetics, 17(4), 377-89, July 1991
 - Tuck A B, Wilson S M, Khokha R, Chambers A F, Different patterns of gene expression in ras-resistant and ras-sensitive cells., Journal of The National Cancer Institute, 83(7), 485-91, 3 Apr 1991
 - Harris J F, Chambers A F, Tam A S, Modulation of clonal progression in B16F1 melanoma cells., Clinical and Experimental Metastasis, 9(2), 151-62, March 1991
 - Tuck A B, Wilson S M, Chambers A F, Resistance of murine LTA cells to oncogene--mediated progression from tumorigenic to metastatic phenotype., Anticancer Research, 10(6), 1507-14, November 1990
 - Tuck A B, Wilson S M, Chambers A F, ras transfection and expression does not induce progression from tumorigenicity to metastatic ability in mouse LTA cells., Clinical and Experimental Metastasis, 8(5), 417-31, September 1990
 - Craig A M, Bowden G T, Chambers A F, Spearman M A, Greenberg A H, Wright J A, McLeod M, Denhardt D T, Secreted phosphoprotein mRNA is induced during multi-stage carcinogenesis in mouse skin and correlates with the metastatic potential of murine fibroblasts., International Journal of Cancer, 46(1), 133-7, 15 Jul 1990
 - Guo X J, Chambers A F, Parfett C L, Waterhouse P, Murphy L C, Reid R E, Craig A M, Edwards D R, Denhardt D T, Identification of a serum-inducible messenger RNA (5B10) as the mouse homologue of calcyclin: tissue distribution and expression in metastatic, ras-transformed NIH 3T3 cells., Cell Growth and Differentiation, 1(7), 333-8, July 1990
 - Chambers A F, Wilson S M, Tuck A B, Denhardt G H, Cairncross J G, Comparison of metastatic properties of a variety of mouse, rat, and human cells in assays in nude mice and chick embryos., In Vivo, 4(4), 215-9, July 1990
 - Harris J F, Chambers A F, Tam A S, Some ras-transformed cells have increased radiosensitivity and decreased repair of sublethal radiation damage., Somatic Cell and Molecular Genetics, 16(1), 39-48, January 1990
 - Chambers A F, Denhardt G H, Wilson S M, ras-transformed NIH 3T3 cell lines, selected for metastatic ability in chick embryos, have increased proportions of p21-expressing cells and are metastatic in nude mice., Invasion and Metastasis, 10(4), 225-40, 1990
 - Tuck, A.B., S.M. Wilson, R. Khokha, and A.F. Chambers, 1991, Different patterns of gene expression in ras-resistant and ras-sensitive cells. Journal of the National Cancer Institute 83:485-491
- Harris, J.F., A.F. Chambers, and A.S.K. Tam, 1990, Some ras transformed cells have increased radiosensitivity and decreased repair of sublethal radiation damage, Somatic Cell and Molecular Genetics 16: 39-48
- Chambers, A.F., G.H. Denhardt, and S.M. Wilson, 1990, Ras-transformed NIH 3T3 cell lines, selected for metastatic ability in chick embryos, have increased proportions of p21-expressing cells and are metastatic in nude mice, Invasion and Metastasis, 10: 225-240
- Craig, A.M., G.T. Bowden, A.F. Chambers, S. Egan, A.H. Greenberg, J. Wright, M. McLeod, and D.T. Denhardt, Secreted phosphoprotein mRNA is induced during multistage carcinogenesis in mouse skin and correlates with the metastatic potential of murine fibroblasts, International Journal of Cancer, 46: 133-137, 1990
- Hill, S.A., S. Wilson and A.F. Chambers, 1988, Clonal heterogeneity, experimental metastatic ability, and p21 expression in H-ras-transformed NIH 3T3 cells, Journal of the National Cancer Institute 80: 484-490
Profile DetailsIndividual Expertise profile of Ann F. Chambers, Copyright Ann F. Chambers. © COS Expertise TM, 2010, ProQuest LLC All rights reserved. |