Andries Zijlstra, Ph.D.
Assistant Professor of Pathology, Microbiology and Immunology
Assistant Professor of Cancer Biology
Vanderbilt University Dept. of Pathology
1161 21st Ave. S., C-2104A MCN
Nashville , TN 37232-2561
Understanding and targeting tumor cell adhesion and migration in cancer metastasis
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 optical imaging strategies using fluorescent and luminescent proteins to visualize cell behavior along the metastatic cascade in vivo. In addition to visualizing the temporal and spatial dymics of metastasis, we implement imaging and biochemical strategies to assess quantitatively how metastasis is impacted by specific mechanisms of motility.
- Hansen, AG, Arnold, SA, Jiang, M, Palmer, TD, Ketova, T, Merkel, A, Pickup, M, Samaras, S, Shyr, Y, Moses, HL, Hayward, SW, Sterling, JA, Zijlstra, A ALCAM/CD166 is a TGF-¿¿-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res, 74(5), 1404-15, 2014.
- Madamanchi, A, Zijlstra, A, Zutter, MM Flipping the switch: integrin switching provides metastatic competence. Sci Signal, 7(318), pe9, 2014.
- Palmer, TD, Mart¿¿nez, CH, Vasquez, C, Hebron, KE, Jones-Paris, C, Arnold, SA, Chan, SM, Chalasani, V, Gomez-Lemus, JA, Williams, AK, Chin, JL, Giannico, GA, Ketova, T, Lewis, JD, Zijlstra, A Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. Cancer Res, 74(1), 173-87, 2014.
- Irvin, MW, Zijlstra, A, Wikswo, JP, Pozzi, A Techniques and assays for the study of angiogenesis. Exp Biol Med (Maywood), 2014.
- Hansen, AG, Freeman, TJ, Arnold, SA, Starchenko, A, Jones-Paris, CR, Gilger, MA, Washington, MK, Fan, KH, Shyr, Y, Beauchamp, RD, Zijlstra, A Elevated ALCAM shedding in colorectal cancer correlates with poor patient outcome. Cancer Res, 73(10), 2955-64, 2013.
- Ashby, WJ, Zijlstra, A Established and novel methods of interrogating two-dimensional cell migration. Integr Biol (Camb), 4(11), 1338-50, 2012.
- Matise, LA, Palmer, TD, Ashby, WJ, Nashabi, A, Chytil, A, Aakre, M, Pickup, MW, Gorska, AE, Zijlstra, A, Moses, HL Lack of transforming growth factor-¿¿ signaling promotes collective cancer cell invasion through tumor-stromal crosstalk. Breast Cancer Res, 14(4), R98, 2012.
- Ashby, WJ, Wikswo, JP, Zijlstra, A Magnetically attachable stencils and the non-destructive analysis of the contribution made by the underlying matrix to cell migration. Biomaterials, 33(33), 8189-203, 2012.
- Campbell, JP, Karolak, MR, Ma, Y, Perrien, DS, Masood-Campbell, SK, Penner, NL, Munoz, SA, Zijlstra, A, Yang, X, Sterling, JA, Elefteriou, F Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice. PLoS Biol, 10(7), e1001363, 2012.
- Gao, Y, Majumdar, D, Jovanovic, B, Shaifer, C, Lin, PC, Zijlstra, A, Webb, DJ, Li, D A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology. Biomed Microdevices, 13(3), 539-48, 2011.
- Palmer, TD, Lewis, J, Zijlstra, A Quantitative Analysis of Cancer Metastasis using an Avian Embryo Model. J Vis Exp, (51), 2011.
- Palmer, TD, Ashby, WJ, Lewis, JD, Zijlstra, A Targeting tumor cell motility to prevent metastasis. Adv Drug Deliv Rev, 63(8), 568-81, 2011.
- Ramirez, NE, Zhang, Z, Madamanchi, A, Boyd, KL, O''Rear, LD, Nashabi, A, Li, Z, Dupont, WD, Zijlstra, A, Zutter, MM The Î±â‚‚Î²â‚ integrin is a metastasis suppressor in mouse models and human cancer. J Clin Invest, 121(1), 226-37, 2011.
- Andries Zijlstra Tetraspanins in Cancer. In: Cell-Extracellular Matrix Interactions in Cancer, Springer Science + Business Media(1st Ed.), 217-244, 2010.
- Zijlstra, A Launching an academic research career. Dis Model Mech, 2(11-12), 526-30, 2009.
- Zijlstra, A, Lewis, J, Degryse, B, Stuhlmann, H, Quigley, JP The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151. Cancer Cell, 13(3), 221-34, 2008.
- FÃ©ral, CC, Zijlstra, A, Tkachenko, E, Prager, G, Gardel, ML, Slepak, M, Ginsberg, MH CD98hc (SLC3A2) participates in fibronectin matrix assembly by mediating integrin signaling. J Cell Biol, 178(4), 701-11, 2007.
- Zijlstra, A, Seandel, M, Kupriyanova, TA, Partridge, JJ, Madsen, MA, Hahn-Dantona, EA, Quigley, JP, Deryugina, EI Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells. Blood, 107(1), 317-27, 2006.
- Zijlstra, A, Quigley, JP The DARC side of metastasis: shining a light on KAI1-mediated metastasis suppression in the vascular tunnel. Cancer Cell, 10(3), 177-8, 2006.
- Lewis, JD, Destito, G, Zijlstra, A, Gonzalez, MJ, Quigley, JP, Manchester, M, Stuhlmann, H Viral nanoparticles as tools for intravital vascular imaging. Nat Med, 12(3), 354-60, 2006.
- Blancafort, P, Chen, EI, Gonzalez, B, Bergquist, S, Zijlstra, A, Guthy, D, Brachat, A, Brakenhoff, RH, Quigley, JP, Erdmann, D, Barbas, CF Genetic reprogramming of tumor cells by zinc finger transcription factors. Proc Natl Acad Sci U S A, 102(33), 11716-21, 2005.
- Wilson, S, Greer, B, Hooper, J, Zijlstra, A, Walker, B, Quigley, J, Hawthorne, S The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. Biochem J, 388(Pt 3), 967-72, 2005.
- Deryugina, EI, Zijlstra, A, Partridge, JJ, Kupriyanova, TA, Madsen, MA, Papagiannakopoulos, T, Quigley, JP Unexpected effect of matrix metalloproteinase down-regulation on vascular intravasation and metastasis of human fibrosarcoma cells selected in vivo for high rates of dissemination. Cancer Res, 65(23), 10959-69, 2005.
- Zijlstra, A, Aimes, RT, Zhu, D, Regazzoni, K, Kupriyanova, T, Seandel, M, Deryugina, EI, Quigley, JP Collagenolysis-dependent angiogenesis mediated by matrix metalloproteinase-13 (collagenase-3). J Biol Chem, 279(26), 27633-45, 2004.
- Aimes, RT, Zijlstra, A, Hooper, JD, Ogbourne, SM, Sit, ML, Fuchs, S, Gotley, DC, Quigley, JP, Antalis, TM Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thromb Haemost, 89(3), 561-72, 2003.
- Hooper, JD, Zijlstra, A, Aimes, RT, Liang, H, Claassen, GF, Tarin, D, Testa, JE, Quigley, JP Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen. Oncogene, 22(12), 1783-94, 2003.
- Zijlstra, A, Testa, JE, Quigley, JP Targeting the proteome/epitome, implementation of subtractive immunization. Biochem Biophys Res Commun, 303(3), 733-44, 2003.
- Zijlstra, A, Mellor, R, Panzarella, G, Aimes, RT, Hooper, JD, Marchenko, ND, Quigley, JP A quantitative analysis of rate-limiting steps in the metastatic cascade using human-specific real-time polymerase chain reaction. Cancer Res, 62(23), 7083-92, 2002.
- Balza, E, Castellani, P, Zijlstra, A, Neri, D, Zardi, L, Siri, A Lack of specificity of endoglin expression for tumor blood vessels. Int J Cancer, 94(4), 579-85, 2001.
- Zijlstra, A, Schelling, ME Detection of multiple fibronectin isoforms in fetal fibroblast monolayer culture: a novel method for the qualitative and quantitative detection of multiple antigens. Histochem Cell Biol, 111(2), 163-9, 1999.
- Zijlstra, A, McCabe, NR, Schelling, ME Expression and assembly of the angiogenic marker B-fibronectin by endothelial cells in vitro: regulation by confluency. Angiogenesis, 3(1), 77-87, 1999.