Vanderbilt University Medical Center
Cancer Metastasis is the primary cause of cancer-related deaths. Research in the laboratory is dedicated to understanding the molecular biology of cancer metastasis and translating this knowledge to clinical application.
The research program is based on three central themes: A) Investigating the molecular mechanisms of tumor cell migration, B) Evaluating and validating these mechanisms in the patient population, and C) developing research and clinical tools to advance our studies.
The laboratory pursues three primary research objectives: 1) Characterization of the molecular mechanism of migration regulated by the tetraspanin CD151, 2) Identification and characterization of the metastatic cell population within a primary tumor, and 3) clinical implementation of molecular markers of migration as biomarkers of tumor progression and metastasis.
Specific mechanistic studies include:
The regulation of migration by tetraspanins: Among the molecular regulators of motility, we have found the tetraspanin CD151 to be a particularly critical component of metastasis. Interfering with its function through antibody binding inhibits extracellular matrix mediated migration and blocks >95% of the tumor cell dissemination in a spontaneous metastasis model. Using a newly-established in vivo motility assay, we have been able to demonstrate that altering the function of CD151 results in complete inhibition of in vivo motility for several tumor cell types. Ongoing studies try to determine the molecular mechanism by which this regulation of migration occurs.
Specific translational studies include:
Molecular mechanisms of migration contribute to metastasis and subsequently thought to be central to the cancer progression poor clinical outcome for cancer patients. We have developed a series of preclinical tests that determine the status of pro migratory mechanisms within the tumor. Using this technology it becomes possible to diagnose patients with aggressive disease, predict clinical outcome, and possible anticipate treatment response. Ongoing studies are expanding biomarker studies to a variety of cancers, including renal, bladder, prostate, lung, and breast cancer.
Specific technological advances:
We have developed novel intravital imaging strategies using the chick embryo to visualize cell behavior along the metastatic cascade in vivo. Quantitative analysis of metastasis have been implemented using species-specific PCR. Most recently we have developed a unique in vitro methodology called Magnetically Attachable Stencils (MAts) which make it possible to determine the contribution that the underlying matrix makes to cell migration. MAts are widely adapted in the VU community for the analysis of cell migration in vitro.
Andries Zijlstra, Rebecca Mellor, Giano Panzarella, Ronald T. Aimes, John D. Hooper, Natalia D. Marchenko, and James P. Quigley. (2002) A Quantitative Analysis of Rate Limiting Steps in the Metastatic Cascade using human specific real-time PCR. Cancer Research, 62: 7083-7092. (PMID: 12460930)
E. Balza, P. Castellani, A. Zijlstra, D. Neri, L. Zardi, A. Siri. (2001) Lack of specificity of endoglin expression for tumor blood vessels. International J. of Cancer, 94(4): 579-85.
Susan Wilson, Brett Greer, John Hooper, Andries Zijlstra, James P. Quigley, Susan Hawthorn. (2005) The membrane-anchored serine protease TMPRSS-2 activates PAR-2 in prostate cancer cells. Biochem. J., 399(3) 967-972
John D. Hooper*, Andries Zijlstra*, Ronald T. Aimes*, Hongyan Liang, Gisela F. Claassen, Jacqueline E. Testa, David Tarin and James P. Quigley. (2003) Subtractive immunization using highly metastatic human tumor cells identifies SIMA-135/CDCP1, a 135kDa Cell surface phosphorylated glycoprotein antigen. Oncogene, 22: 1783-1794.
Ronald T. Aimes*, Andries Zijlstra*, John D. Hooper*, Steven M. Ogbourne, Mae-le Sit, Simone Fuchs, David C. Gotley, James P. Quigley, and Toni M. Antalis. (2003) Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thrombosis and Haemostasis, 89: 561-72.
Andries Zijlstra*, Ronald T. Aimes*, Dan Zhu, Karine Regazzoni, Marco Seandel, Elena I. Deryugina and James P. Quigley. (2004) Collagenolysis-dependent angiogenesis mediated by matrix metalloproteinase-13 (collagenase-3). Journal of Biological Chemistry, 279(26): 27633-45. (PMID: 15066996)
Elena I. Deryugina*, Andries Zijlstra*, Junith Partridge, Tatyana A. Kupriyanova, Mark Madson, Thales Papagiannakopoulos, and James P. Quigley. (2005) Unexpected Effect of Matrix Metalloproteinase Downregulation on Vascular Intravasation and Metastasis of Human Fibrosarcoma Cells selected in vivo for High Rates of Dissemination. Cancer Research Dec 1;65(23):10959-69. (PMID: 16322244)
Pilar Blancafort, Emily Chen, Beatriz Gonzalez, Sharon Bergquist, Andries Zijlstra, James P. Quigley, Caren V. Lund, Ruud Brakenhoff, Dirk Edrmann and Carlos F. Barbas III. (2005) Genetic Reprogramming of Tumor Cells by Artificial Transcription Factors. Proc Natl Acad Sci USA, 102(33):11716-21
Lewis, J.D., Destito, G., Zijlstra, A., Gonzalez, M.J., Quigley, J.P., Manchester, M., and Stuhlmann, H. (2006). Viral nanoparticles as tools for intravital vascular imaging. Nature Med., March vol. 12 (3) pp. 354-60.
- Andries Zijlstra, Marco Seandal, Elisabeth A. Hahn-Dantona, Tatyana Kupriyanova, Juneth Partridge, James P. Quigley and Elena I. Deryugina. (2006) Pro-angiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells. Blood, Jan 1;107 (1):317-27. (PMID: 16174763)
- Andries Zijlstra and James P. Quigley (2006) The DARC side of metastasis: shining a light on KAI1-mediated metastasis suppression in the vascular tunnel. Cancer Cell Sept (10), 177-178. (PMID: 16959609)
- Chloe Feral, Andries Zijlstra, Gerald Prager, Marina Slepak, Mark H. Ginsberg (2007) CD98hc (SLC3A2) Mediates Fibronectin Matrix Assembly, JCB, Aug 13;178(4):701-11. (PMID: 17682053)
- Andries Zijlstra, John Lewis, Bernard DeGryse, Heidi Stuhlmann, and James P. Quigley (2008) The inhibition of tumor cell intravasation and subsequent metastasis through the regulation of in vivo tumor cell motility by the tetraspanin CD151, Cancer Cell, March 13 (3) pp. 221-34. (PMID: 18328426)
- Hon Sing Leong, Nicole F. Steinmetz, Amber Ablack, Giuseppe Destito, Andries Zijlstra, Heidi Stuhlmann, Marianne Manchester, John D. Lewis (2010) Viral nanoparticles as a platform for intravital imaging of embryonic and tumor neovasculature. Nature Protocols, 5, 1406–1417 (PMID: 20671724)
- Norma E. Ramirez, Zhonghua Zhang, Aasakiran Madamanchi, Kelli L. Boyd, Lynda D. O’Rear, Abudi Nashabi, Zhengzi Li, William D. Dupont, Andries Zijlstra, and Mary M. Zutter. (2010) The α2β1 integrin is a metastasis suppressor in mouse models and human cancer. Journal of Clinical Investigations, Jan;121(1):226-37 (PMID: 21135504)
- Yi Zhang, Wendy Schulte, Desmond Pink, Andries Zijlstra, John Lewis, and David Morton Waisman (2010) Sensitivity of Cancer Cells to Truncated Diphtheria Toxin. PLOS ONE, 5(5):e10498. (PMID: 20463924)
- Yandong Gao,Devi Majumdar,Bojana Jovanovic, Candice Shaifer, P. Charles Lin, Andries Zijlstra, Donna J. Webb, and Deyu Li. (2011) A Versatile Valve-Enabled Microfluidic Cell Co-Culture Platform and Demonstration of its Applications to Neurobiology and Cancer Biology. Biomedical Microdevices, 13(3), 539–548. doi:10.1007/s10544-011-9523-9 (PMID: 21424383)
- Choi-Fong Cho, Amber Ablack, Hon-Sing Leong, Andries Zijlstra, and John Lewis. (2011) Evaluation of nanoparticle uptake in tumors in real time using intravital imaging. Journal of visualized experiments : JoVE, (52), e2808. (PMID: 21730939)
- Desmond B.S. Pink, Wendy Schulte, Missag H. Parseghian, Andries Zijlstra, John D. Lewis(2012) Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery. PLoS ONE 7(3): e33760. doi:10.1371/journal.pone.0033760 (PMID: 22479438)
- Trenis Palmer and Andries Zijlstra (2011) CD151. UCSD-Nature Molecule Pages (doi:10.1038/mp.a004123.01)
- Amanda G. Hansen, Guido W. Swart, and Andries Zijlstra (2011) ALCAM. UCSD-Nature Molecule Pages (doi:10.1038/mp.a004126.01)
- Trenis D. Palmer, John D. Lewis, and Andries Zijlstra (2011) Quantitative analysis of cancer metastasis using an avian embryo model. Journal of visualized experiments : JoVE, (51), e2815. (PMID: 21673636)
- Trenis D. Palmer, William Ashby, John D. Lewis, and Andries Zijlstra (2011) Targeting Tumor Cell Motility and Metastasis. Advanced Drug Delivery Reviews, 63(8), 568–581. doi:10.1016/j.addr.2011.04.008 (PMID: 21664937)
- William J. Ashby and Andries Zijlstra (2012) Established and Novel Methods of Interrogating Two-Dimensional Cell Migration. Integrative Biology 4(11):1338–1350. PMID: 23038152
- AJ. Preston Campbell, Matthew R. Karolak, Yun Ma, Daniel S. Perrien, S. Kathryn Masood-Campbell, Steve A. Munoz, Andries Zijlstra, Xiangli Yang, Julie A. Sterling and Florent Elefteriou. (2012) Activation of Sympathetic Nerves in Mice Promotes Breast Cancer Bone Metastasis via RANKL. PLOS Biology, 10(7), e1001363. doi:10.1371/journal.pbio.1001363 (PMID: 22815651)
- William J. Ashby, John P. Wikswo, Andries Zijlstra(2012) Magnetically attachable stencils and the non-destructive analysis of the contribution made by the underlying matrix to cell migration. Biomaterials, 33(33), 8189–8203. (doi:10.1016/j.biomaterials.2012.07.018) PMID: 22940214
- Amanda G. Hansen, Tanner J. Freeman, Shanna A. Arnold, Alina Starchenko, Celestial R. Jones-Paris, Michael A. Gilger, Mary K. Washington, Kang-Hsien Fan, Yu Shyr, Robert D. Beauchamp and Andries Zijlstra.(2013) Elevated ALCAM shedding in colorectal cancer correlates with poor patient outcome. Cancer Research 73(10): 2955–2964. (doi: 10.1158/0008-5472.CAN-12-2052) PMID: 23539446/PMC3660148
- Lauren A. Matise, Trenis D. Palmer, William J. Ashby, Abudi Nashabi, Anna Chytil, Mary Aakre, Michael W. Pickup, Andries Zijlstra and Harold L. Moses.(2012) Lack of TGF-β signaling promotes collective cancer cell invasion in tumor-stromal crosstalk. Breast Cancer Research, 14(4), R98. doi:10.1186/bcr3217 (PMID: 22748014)
- William J. Ashby, John P. Wikswo, and Andries Zijlstra (2013) Magnetically Attachable Templates: Taking the Punch Out of PDMS Microfluidic Interconnects. The Open Biomedical Engineering Journal (accepted)
- Trenis D. Palmer, Carlos H. Martínez, Catalina Vasquez, Celestial R. Jones-Paris, Katie Hebron, Susanne M. Chan, Venu Chalasani, Jose A. Gomez-Lemus, Andrew K. Williams, Joseph L. Chin, Tatiana Ketova, John D. Lewis and Andries Zijlstra (2013) Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. Cancer Research (in Press)
Invited Chapters and Reviews
- Andries Zijlstra, Jacqueline E. Testa, and James P. Quigley. (2003) Targeting the proteome/epitome, implementation of subtractive immunization. Biochemical and Biophysical Research Communications, 303: 733-744.
- Zijlstra, A., Mikolon D.M. and D.G. Stupack. (2007) Angiogenesis Assays in the Chick. In: Angiogenesis Assays: a critical appraisal of current techniques. Eds: Staton CA, Lewis CE, Bicknell R. John Wiley & Sons.
- Andries Zijlstra (2009) Launching and Academic Research Career. Dis Model Mech. 2009 Nov-Dec;2(11-12):526-30.
- Andries Zijlstra (2009) Tetraspanins in Cancer. In: Cell-Extracellular Matrix Interactions in Cancer. Ed. Zent, R and Pozzi, A. Springer Science and Business Media
- Andries Zijlstra and John D. Lewis. (2012). Visualization and quantification of de novo angiogenesis in ex ovo chicken embryos. The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications. (eds. Zudaire, E. and Cuttitta, F. Dordrecht: Springer Netherlands.
- Kristin Kain, James Miller, John D. Lewis, David Bader, Joey Barnett, Andries Zijlstra The chick embryo: a proven model for human physiology and disease. Developmental Dynamics. (In Press)