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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 

Andries Zijlstra, Ph.D.

Assistant Professor of Pathology, Microbiology and Immunology
Assistant Professor of Cancer Biology
Researcher

Contact Information:

Vanderbilt University Dept. of Pathology
1161 21st Ave. S., C-2104A MCN
Nashville , TN 37232-2561
615-322-3295
Fax: 615-936-7040

Research Description

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.

Publications
  • Arnold SA, Loomans HA, Ketova T, Andl CD, Clark PE, Zijlstra A. Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer. Clin. Exp. Metastasis [print-electronic]. 2015 Oct 10/11/2015; PMID: 26456754, PII: 10.1007/s10585-015-9754-x, DOI: 10.1007/s10585-015-9754-x, ISSN: 1573-7276.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26456754.
  • An H, Stoops SL, Deane NG, Zhu J, Zi J, Weaver C, Waterson AG, Zijlstra A, Lindsley CW, Beauchamp RD. Small molecule/ML327 mediated transcriptional de-repression of E-cadherin and inhibition of epithelial-to-mesenchymal transition. Oncotarget. 2015 Sep 9/8/2015; 6(26): 22934-48. PMID: 26082441, PMCID: PMC4673210, PII: 4473, DOI: 10.18632/oncotarget.4473, ISSN: 1949-2553.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26082441.
  • Nakamura T, Shinriki S, Jono H, Guo J, Ueda M, Hayashi M, Yamashita S, Zijlstra A, Nakayama H, Hiraki A, Shinohara M, Ando Y. Intrinsic TGF-ß2-triggered SDF-1-CXCR4 signaling axis is crucial for drug resistance and a slow-cycling state in bone marrow-disseminated tumor cells. Oncotarget. 2015 Jan 1/20/2015; 6(2): 1008-19. PMID: 25504440, PMCID: PMC4359213, PII: 2826, DOI: 10.18632/oncotarget.2826, ISSN: 1949-2553.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25504440.
  • Preston Campbell J, Mulcrone P, Masood SK, Karolak M, Merkel A, Hebron K, Zijlstra A, Sterling J, Elefteriou F. TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton. Sci Rep. 2015; 5: 12635. PMID: 26271202, PMCID: PMC4536516, PII: srep12635, DOI: 10.1038/srep12635, ISSN: 2045-2322.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26271202.
  • Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM. Directional cell movement through tissues is controlled by exosome secretion. Nat Commun. 2015; 6: 7164. PMID: 25968605, PMCID: PMC4435734, PII: ncomms8164, DOI: 10.1038/ncomms8164, ISSN: 2041-1723.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25968605.
  • Irvin MW, Zijlstra A, Wikswo JP, Pozzi A. Techniques and assays for the study of angiogenesis. Exp. Biol. Med. (Maywood) [print-electronic]. 2014 Nov; 239(11): 1476-88. PMID: 24872440, PMCID: PMC4216737, PII: 1535370214529386, DOI: 10.1177/1535370214529386, ISSN: 1535-3699.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24872440.
  • Stoletov K, Bond D, Hebron K, Raha S, Zijlstra A, Lewis JD. Metastasis as a therapeutic target in prostate cancer: a conceptual framework. Am J Clin Exp Urol. 2014 Apr; 2(1): 45-56. PMID: 25360439, PMCID: PMC4219290, ISSN: 2330-1910.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25360439.
  • Madamanchi A, Zijlstra A, Zutter MM. Flipping the switch: integrin switching provides metastatic competence. Sci Signal. 2014 Mar 3/25/2014; 7(318): pe9. PMID: 24667375, PMCID: PMC4209128, PII: 7/318/pe9, DOI: 10.1126/scisignal.2005236, ISSN: 1937-9145.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24667375.
  • 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-ß-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res [print-electronic]. 2014 Mar 3/1/2014; 74(5): 1404-15. PMID: 24385212, PMCID: PMC4149913, PII: 0008-5472.CAN-13-1296, DOI: 10.1158/0008-5472.CAN-13-1296, ISSN: 1538-7445.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24385212.
  • Kain KH, Miller JW, Jones-Paris CR, Thomason RT, Lewis JD, Bader DM, Barnett JV, Zijlstra A. The chick embryo as an expanding experimental model for cancer and cardiovascular research. Dev. Dyn [print-electronic]. 2014 Feb; 243(2): 216-28. PMID: 24357262, PMCID: PMC4164046, DOI: 10.1002/dvdy.24093, ISSN: 1097-0177.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24357262.
  • Palmer TD, Martínez 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 [print-electronic]. 2014 Jan 1/1/2014; 74(1): 173-87. PMID: 24220242, PMCID: PMC3947299, PII: 0008-5472.CAN-13-0275, DOI: 10.1158/0008-5472.CAN-13-0275, ISSN: 1538-7445.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24220242.
  • Jovanovic B, Beeler JS, Pickup MW, Chytil A, Gorska AE, Ashby WJ, Lehmann BD, Zijlstra A, Pietenpol JA, Moses HL. Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer. Breast Cancer Res. 2014; 16(4): R69. PMID: 24985072, PMCID: PMC4095685, PII: bcr3684, DOI: 10.1186/bcr3684, ISSN: 1465-542X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24985072.
  • 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 [print-electronic]. 2013 May 5/15/2013; 73(10): 2955-64. PMID: 23539446, PMCID: PMC3660148, PII: 0008-5472.CAN-12-2052, DOI: 10.1158/0008-5472.CAN-12-2052, ISSN: 1538-7445.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23539446.
  • 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 [print-electronic]. 2012 Nov; 33(33): 8189-203. PMID: 22940214, PMCID: PMC3444626, PII: S0142-9612(12)00787-9, DOI: 10.1016/j.biomaterials.2012.07.018, ISSN: 1878-5905.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22940214.
  • Ashby WJ, Zijlstra A. Established and novel methods of interrogating two-dimensional cell migration. Integr Biol (Camb). 2012 Nov; 4(11): 1338-50. PMID: 23038152, PMCID: PMC4165521, DOI: 10.1039/c2ib20154b, ISSN: 1757-9708.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23038152.
  • 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 [print-electronic]. 2012 Jul; 10(7): e1001363. PMID: 22815651, PMCID: PMC3398959, PII: PBIOLOGY-D-12-00249, DOI: 10.1371/journal.pbio.1001363, ISSN: 1545-7885.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22815651.
  • 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-ß signaling promotes collective cancer cell invasion through tumor-stromal crosstalk. Breast Cancer Res. 2012; 14(4): R98. PMID: 22748014, PMCID: PMC3680921, PII: bcr3217, DOI: 10.1186/bcr3217, ISSN: 1465-542X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22748014.
  • Palmer TD, Ashby WJ, Lewis JD, Zijlstra A. Targeting tumor cell motility to prevent metastasis. Adv. Drug Deliv. Rev [print-electronic]. 2011 Jul 7/18/2011; 63(8): 568-81. PMID: 21664937, PMCID: PMC3132821, PII: S0169-409X(11)00133-5, DOI: 10.1016/j.addr.2011.04.008, ISSN: 1872-8294.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21664937.
  • 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. 2011 Jun; 13(3): 539-48. PMID: 21424383, PMCID: PMC3085600, DOI: 10.1007/s10544-011-9523-9, ISSN: 1572-8781.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21424383.
  • Ramirez NE, Zhang Z, Madamanchi A, Boyd KL, O'Rear LD, Nashabi A, Li Z, Dupont WD, Zijlstra A, Zutter MM. The a2ß1 integrin is a metastasis suppressor in mouse models and human cancer. J. Clin. Invest [print-electronic]. 2011 Jan; 121(1): 226-37. PMID: 21135504, PMCID: PMC3007139, PII: 42328, DOI: 10.1172/JCI42328, ISSN: 1558-8238.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21135504.
  • Cho CF, Ablack A, Leong HS, Zijlstra A, Lewis J. Evaluation of nanoparticle uptake in tumors in real time using intravital imaging. J Vis Exp. 2011; (52): PMID: 21730939, PMCID: PMC3197055, PII: 2808, DOI: 10.3791/2808, ISSN: 1940-087X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21730939.
  • Hansen AG, Swart GW, Zijlstra A. ALCAM: Basis Sequence: Mouse. AFCS Nat Mol Pages. 2011; 2011: PMID: 25983661, PMCID: PMC4432864, ISSN: 1477-5921.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25983661.
  • Palmer TD, Lewis J, Zijlstra A. Quantitative analysis of cancer metastasis using an avian embryo model. J Vis Exp. 2011; (51): PMID: 21673636, PMCID: PMC3197130, PII: 2815, DOI: 10.3791/2815, ISSN: 1940-087X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21673636.
  • Palmer TD, Zijlstra A. CD151: Basis Sequence: Mouse. AFCS Nat Mol Pages. 2011; 2011: PMID: 25983660, PMCID: PMC4432845, ISSN: 1477-5921.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25983660.
  • Leong HS, Steinmetz NF, Ablack A, Destito G, Zijlstra A, Stuhlmann H, Manchester M, Lewis JD. Intravital imaging of embryonic and tumor neovasculature using viral nanoparticles. Nat Protoc [print-electronic]. 2010 Aug; 5(8): 1406-17. PMID: 20671724, PMCID: PMC3163450, PII: nprot.2010.103, DOI: 10.1038/nprot.2010.103, ISSN: 1750-2799.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20671724.
  • Andries Zijlstra. In: Cell-Extracellular Matrix Interactions in Cancer. [place unknown: publisher unknown]; 2010. (Springer Science + Business Media).
    Available from: http://www.springer.com/biomed/cancer/book/978-1-4419-0813-1.
  • Zhang Y, Schulte W, Pink D, Phipps K, Zijlstra A, Lewis JD, Waisman DM. Sensitivity of cancer cells to truncated diphtheria toxin. PLoS ONE. 2010; 5(5): e10498. PMID: 20463924, PMCID: PMC2864767, DOI: 10.1371/journal.pone.0010498, ISSN: 1932-6203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20463924.
  • Zijlstra A. Launching an academic research career [editorial]. Dis Model Mech. 2009 Nov; 2(11-12): 526-30. PMID: 19892881, PII: 2/11-12/526, DOI: 10.1242/dmm.004523, ISSN: 1754-8411.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19892881.
  • 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. 2008 Mar; 13(3): 221-34. PMID: 18328426, PMCID: PMC3068919, PII: S1535-6108(08)00040-8, DOI: 10.1016/j.ccr.2008.01.031, ISSN: 1878-3686.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18328426.
  • Féral 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 [print-electronic]. 2007 Aug 8/13/2007; 178(4): 701-11. PMID: 17682053, PMCID: PMC2064475, PII: jcb.200705090, DOI: 10.1083/jcb.200705090, ISSN: 0021-9525.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17682053.
  • Zijlstra A, Quigley JP. The DARC side of metastasis: shining a light on KAI1-mediated metastasis suppression in the vascular tunnel. Cancer Cell. 2006 Sep; 10(3): 177-8. PMID: 16959609, PII: S1535-6108(06)00252-2, DOI: 10.1016/j.ccr.2006.08.012, ISSN: 1535-6108.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16959609.
  • Lewis JD, Destito G, Zijlstra A, Gonzalez MJ, Quigley JP, Manchester M, Stuhlmann H. Viral nanoparticles as tools for intravital vascular imaging. Nat. Med [print-electronic]. 2006 Mar; 12(3): 354-60. PMID: 16501571, PMCID: PMC2536493, PII: nm1368, DOI: 10.1038/nm1368, ISSN: 1078-8956.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16501571.
  • 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 [print-electronic]. 2006 Jan 1/1/2006; 107(1): 317-27. PMID: 16174763, PMCID: PMC1895349, PII: 2005-04-1458, DOI: 10.1182/blood-2005-04-1458, ISSN: 0006-4971.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16174763.
  • 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. 2005 Dec 12/1/2005; 65(23): 10959-69. PMID: 16322244, PII: 65/23/10959, DOI: 10.1158/0008-5472.CAN-05-2228, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16322244.
  • 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 [print-electronic]. 2005 Aug 8/16/2005; 102(33): 11716-21. PMID: 16081541, PMCID: PMC1187960, PII: 0501162102, DOI: 10.1073/pnas.0501162102, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16081541.
  • 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. 2005 Jun 6/15/2005; 388(Pt 3): 967-72. PMID: 15537383, PMCID: PMC1183478, PII: BJ20041066, DOI: 10.1042/BJ20041066, ISSN: 1470-8728.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15537383.
  • 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 [print-electronic]. 2004 Jun 6/25/2004; 279(26): 27633-45. PMID: 15066996, PII: M313617200, DOI: 10.1074/jbc.M313617200, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15066996.
  • Zijlstra A, Testa JE, Quigley JP. Targeting the proteome/epitome, implementation of subtractive immunization. Biochem. Biophys. Res. Commun. 2003 Apr 4/11/2003; 303(3): 733-44. PMID: 12670472, PII: S0006291X03003577, ISSN: 0006-291X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12670472.
  • 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. 2003 Mar 3/27/2003; 22(12): 1783-94. PMID: 12660814, PII: 1206220, DOI: 10.1038/sj.onc.1206220, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12660814.
  • 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. 2003 Mar; 89(3): 561-72. PMID: 12624642, PII: 03030561, DOI: 10.1267/THRO03030561, ISSN: 0340-6245.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12624642.
  • 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. 2002 Dec 12/1/2002; 62(23): 7083-92. PMID: 12460930, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12460930.
  • 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. 2001 Nov; 94(4): 579-85. PMID: 11745447, PII: 10.1002/ijc.1505, ISSN: 0020-7136.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11745447.
  • 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. 1999 Feb; 111(2): 163-9. PMID: 10090577, ISSN: 0948-6143.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10090577.
  • Zijlstra A, McCabe NR, Schelling ME. Expression and assembly of the angiogenic marker B-fibronectin by endothelial cells in vitro: regulation by confluency. Angiogenesis. 1999; 3(1): 77-87. PMID: 14517447, PII: 239971, ISSN: 0969-6970.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14517447.