Magnus Edlund, Ph.D.
Assistant
Professor
Molecular Urology and Therapeutics Program
Department of Urology
Contact Information
Department of Urology
Emory University School of Medicine
Clinic B, Suite 5105
1365 Clifton Road, N.E.
Atlanta, GA 30322
Phone: 404-778-3683
Fax: 404-778-3965
Email: edlund@emory.edu
Education
B.A., Uppsala University ,
Sweden
Ph.D., Medical Nobel Institute, Karolinska Institute, Stockholm , Sweden
Postdoctoral Research, University of Virginia , Departments of Cell Biology
and Urology, Charlottesville , VA
Research Interests
When prostate cancer cells progress from primary tumor to aggressive metastasis, dramatic changes occur in their abilities to communicate with and attach to their surroundings. Our work links the fields of cell-cell communication and cell-matrix adhesion, by focusing on the cell-cell regulation of integrin cell adhesion molecule activities.
My laboratory makes use of
mixed cell co-cultures to reproduce specific cell-cell interactions, while
we study gap-junctional and other forms of connections between the different
cell lines. We assay cell adhesion molecule activities in the co-cultured
cells. Using patient samples, and taking advantage of human prostate cancer
cell lines that represent different stages in cancer progression, we have
chronicled the changes in integrin use (as well as integrin expression)
that accompany cancerous progression, have identified several candidate,
therapeutic targets within the integrin family, and have found that, in
preliminary studies, inhibiting the function of these proteins in mice
hosting prostate tumor cells effectively inhibits tumor growth during
treatment, with immediate relapse when treatment is halted.
We have also begun to explore lipid regulation of cell adhesion function
in prostate cancer cells. Not only may cells use lipid transfer as a means
of cell-cell communication, but microdomains of phospholipids, cholesterol
and glycosphingolipids are arranged non-randomly within the lipid leaflets
of all cells' plasma membranes, creating curvatures and variations in
membrane properties and thicknesses. We are asking whether these variations
result in integrin protein transmembrane domains being exposed to differing
degrees of interaction with kinases and structural cytoskeletal-linking
proteins (which themselves interact only with subsets of lipids). Because
lipid compositions of cell membranes are directly affected by alterable
dietary and environmental factors, we are hopeful that their role in cell
adhesion will provide new therapeutic targets for prostate cancer treatment.
Ongoing Projects
Role of Gap junction Formation During Cancer Progression - This project explores the possibility that homo and heterotypic gap junctions form between the stroma and the cancerous epithelial cells and are crucial for the cancerous progression of reactive stroma.
Vesicle-Mediated Spread of
Phenotype - Not only are cancerous behaviors transferable among a co-culture
of cells, but as cells increase their metastatic behaviors, they release
increasing numbers of shed lipid vesicles into their surroundings. We
are studying the mechanism underlying this shedding, and the possibility
that information contained within these vesicles is spread among neighboring
cells.
Membrane Lipid Regulation of Cell Adhesion - Similar in concept to the
integrin profiles we created for prostate cancer cells at different stages
of disease progression, we have begun to correlate changes in cellular
lipid profiles during disease progression with cell adhesion molecular
functions.
Current Research Group
Amanda Tate, M.S., Research
Specialist (M.S., University of North Carolina)
Michael Schlicht
Publications
1. Knight B, Laukaitis C,
Akhtar N, Hotchin N, Edlund M, and Horwitz AF. Visualizing cell migration
in situ. Current Biol. 10:576-85, 2000.
2. Edlund M, Lotano M, and Otey C. Dynamics of ?-actinin in focal adhesions
and stress fibers visualized with a-actinin-green fluorescent protein
cultured cells. Cell Motil and Cytoskel. 48(3):190-200, 2001.
3. Edlund M, Miyamoto T, Sikes RA, Ogle R, Laurie GW, Farach-Carson MC,
Otey CA, Zhau HE, and Chung, LWK. Integrin expression and utilization
by LNCaP prostate cancer cells on laminin substrata. Cell Growth and Differen.
12(2):99-107, 2001.
4. Cinar B, Koeneman KS, Edlund M, Prins PG, Zhau HE, and Chung LWK. Androgen
receptor mediates the reduced tumor growth, enhanced androgen responsiveness,
and selected target gene transactivation in a human prostate cancer cell
line. Cancer Res. 61(19):7310-7, 2001.
5. Ye QN, Cinar, B, Edlund M, Chung, LWK, Zhau, HE. Inhibition of growth
and cell cycle arrest of ARCaP human prostate cancer cells by ectopic
expression of ER-alpha. Mol. Cellular Biochem. 228: 105-110, 2001.
6. Gonzalez AM, Otey C, Edlund M. and Jones JC. Interactions of a hemidesmosome
component and actinin family members J. Cell Sci. 114, 4197-4206, 2001.
7. Sikes RA, Koeneman KS, Edlund NM, Bissonette EA, Nicholson B, Bradley
MJ, Pienta KJ, amd Chung LWK. Cellular interactions in the tropism of
prostate cancer to bone. Int. J. Cancer 110:4 497-503, 2004.
8. Edlund M, Sung SY and Chung LWK. Modulation of Prostate Cancer Growth
in Bone Microenvironments J. Cellular Biochem. 91:4, 686-705, 2004.
9. Peterson LJ, Rajfur Z, Maddox AS, Freel CD, Chen Y, Edlund M, Otey
C and Burridge K. Simultaneous stretching and contraction of stress fibers
in vivo. Mol Biol Cell 15:7 3497-508. 2004
10. Krueckl SL, Sikes R. E, Edlund NM, Bell R, Hurtado-Coll A, Fazli L,
Gleave ME, and Cox ME. Increased Insulin-like Growth Factor 1 Receptor
Expression and Signaling is a Component of Androgen-independent Progression
in a Lineage-derived Prostate Cancer Progression Model. Cancer Research
64:23 8620-8629, 2004.
11. Knudsen B.S and Edlund M. Prostate cancer and the met hepatocyte growth
factor receptor. Advances in Cancer Research in press vol. 91 July, 2004.
12. Bisanz, K., Yu, J., Edlund, M., Spohn B., Hung, M.C., Chung, L.W.K.
and Hsieh, C.L. Targeting ECM/Integrin Interaction with Liposome-Encapsulated
Small Interfering RNAs Inhibits the Growth of Human Prostate Cancer in
a Bone Xenograft Imaging Model. Mol. Ther. 12:4 634-643, 2005
13. Tate A, Lung T, Radhakrishnan A, and Edlund M. Changes in Gap Junctional
Connexins During Prostate Cancer Progression. Prostate, 66:1, 19-31, 2006.
14. Tate, A., Isotani, S., Bradley, MJ., Sikes, RA., Davis, R., Chung,
LWK and Edlund, M. Met-Independent Hepatocyte Growth Factor Regulation
of Cell Adhesion in Prostate Cancer Cell Lines. Submitted 2006.
15. Choil, W.W.L., Datta, M.W. and Edlund M. Connexin 26 Vesicular
Localization Correlates With Aggressive Prostate Cancer Stage and Grade.
Submitted 2006.