Cancer Metastasis is initiated by the initial dissemination of tumor cells away from the primary tumor. We hypothesize that immobilization of tumor cells through enhanced adhesion can prevent systemic dissemination of tumor cells. A combination of in vivo models, biochemical assays and genetic screens is used to identify and alter the molecular components that can immobilize the metastasizing tumor cell. Using a translational research approach we test and validate the contribution of migratory mechanisms to the progression of cancer in patients. 

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) In vivo screening for molecular mechanism of migration capable of reverting the invasive phenotype of metastastic tumor cells.

 The research program is based on three central themes: A) Investigating the molecular mechanisms of migration, B) Evaluating and validating these mechanisms in the patient population, and C) developing research and clinical tools to advance our studies. 

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:

The evaluation of molecular mechanisms of migration that contribute to metastasis as clinical biomarkers. We aim to identify patients that are likely to progress clinically due to presence molecularly advanced. The focus is on the identification of molecular indicators that are independent of pathological staging in order to identify high risk patients even if they present with early stage or benign disease. Specific emphasis is placed on molecular mechanisms of migration because they can facilitate early dissemination prior to the clinical manifestation of malignant invasion and metastatic lesions.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Modulation of cell adhesion and migration through regulation of the immunoglobulin superfamily member ALCAM/CD166. von Lersner A, Droesen L, Zijlstra A (2019) Clin Exp Metastasis 36(2): 87-95
    › Primary publication · 30778704 (PubMed) · PMC6639050 (PubMed Central)
  2. Beyond the H&E: Advanced Technologies for in situ Tissue Biomarker Imaging. Himmel LE, Hackett TA, Moore JL, Adams WR, Thomas G, Novitskaya T, Caprioli RM, Zijlstra A, Mahadevan-Jansen A, Boyd KL (2018) ILAR J 59(1): 51-65
    › Primary publication · 30462242 (PubMed) · PMC6645175 (PubMed Central)
  3. AXL Mediates Esophageal Adenocarcinoma Cell Invasion through Regulation of Extracellular Acidification and Lysosome Trafficking. Maacha S, Hong J, von Lersner A, Zijlstra A, Belkhiri A (2018) Neoplasia 20(10): 1008-1022
    › Primary publication · 30189359 (PubMed) · PMC6126204 (PubMed Central)
  4. Emerin Deregulation Links Nuclear Shape Instability to Metastatic Potential. Reis-Sobreiro M, Chen JF, Novitskaya T, You S, Morley S, Steadman K, Gill NK, Eskaros A, Rotinen M, Chu CY, Chung LWK, Tanaka H, Yang W, Knudsen BS, Tseng HR, Rowat AC, Posadas EM, Zijlstra A, Di Vizio D, Freeman MR (2018) Cancer Res 78(21): 6086-6097
    › Primary publication · 30154147 (PubMed)
  5. Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. Vagner T, Spinelli C, Minciacchi VR, Balaj L, Zandian M, Conley A, Zijlstra A, Freeman MR, Demichelis F, De S, Posadas EM, Tanaka H, Di Vizio D (2018) J Extracell Vesicles 7(1): 1505403
    › Primary publication · 30108686 (PubMed) · PMC6084494 (PubMed Central)
  6. Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling. Fröse J, Chen MB, Hebron KE, Reinhardt F, Hajal C, Zijlstra A, Kamm RD, Weinberg RA (2018) Cell Rep 24(4): 962-972
    › Primary publication · 30044991 (PubMed) · PMC6181240 (PubMed Central)
  7. Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis. Stoletov K, Willetts L, Paproski RJ, Bond DJ, Raha S, Jovel J, Adam B, Robertson AE, Wong F, Woolner E, Sosnowski DL, Bismar TA, Wong GK, Zijlstra A, Lewis JD (2018) Nat Commun 9(1): 2343
    › Primary publication · 29904055 (PubMed) · PMC6002534 (PubMed Central)
  8. Successful Establishment of Primary Type II Alveolar Epithelium with 3D Organotypic Coculture. Sucre JMS, Jetter CS, Loomans H, Williams J, Plosa EJ, Benjamin JT, Young LR, Kropski JA, Calvi CL, Kook S, Wang P, Gleaves L, Eskaros A, Goetzl L, Blackwell TS, Guttentag SH, Zijlstra A (2018) Am J Respir Cell Mol Biol 59(2): 158-166
    › Primary publication · 29625013 (PubMed) · PMC6096337 (PubMed Central)
  9. Size matters in nanoscale communication. Zijlstra A, Di Vizio D (2018) Nat Cell Biol 20(3): 228-230
    › Primary publication · 29476154 (PubMed) · PMC6652179 (PubMed Central)
  10. Alternative splicing of ALCAM enables tunable regulation of cell-cell adhesion through differential proteolysis. Hebron KE, Li EY, Arnold Egloff SA, von Lersner AK, Taylor C, Houkes J, Flaherty DK, Eskaros A, Stricker TP, Zijlstra A (2018) Sci Rep 8(1): 3208
    › Primary publication · 29453336 (PubMed) · PMC5816644 (PubMed Central)
  11. Loss of ACVRIB leads to increased squamous cell carcinoma aggressiveness through alterations in cell-cell and cell-matrix adhesion proteins. Loomans HA, Arnold SA, Hebron K, Taylor CJ, Zijlstra A, Andl CD (2017) Am J Cancer Res 7(12): 2422-2437
    › Primary publication · 29312797 (PubMed) · PMC5752684 (PubMed Central)
  12. CD318 is a ligand for CD6. Enyindah-Asonye G, Li Y, Ruth JH, Spassov DS, Hebron KE, Zijlstra A, Moasser MM, Wang B, Singer NG, Cui H, Ohara RA, Rasmussen SM, Fox DA, Lin F (2017) Proc Natl Acad Sci U S A 114(33): E6912-E6921
    › Primary publication · 28760953 (PubMed) · PMC5565428 (PubMed Central)
  13. Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading. Tian H, Ketova T, Hardy D, Xu X, Gao X, Zijlstra A, Blobe GC (2017) Arterioscler Thromb Vasc Biol 37(6): 1115-1126
    › Primary publication · 28450296 (PubMed) · PMC5444426 (PubMed Central)
  14. Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed? Minciacchi VR, Zijlstra A, Rubin MA, Di Vizio D (2017) Prostate Cancer Prostatic Dis 20(3): 251-258
    › Primary publication · 28374743 (PubMed) · PMC5569339 (PubMed Central)
  15. Meeting report: Metastasis Research Society-Chinese Tumor Metastasis Society joint conference on metastasis. Bankaitis K, Borriello L, Cox T, Lynch C, Zijlstra A, Fingleton B, Gužvić M, Anderson R, Neman J (2017) Clin Exp Metastasis 34(3-4): 203-213
    › Primary publication · 28260197 (PubMed)
  16. Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging. Sobolik T, Su YJ, Ashby W, Schaffer DK, Wells S, Wikswo JP, Zijlstra A, Richmond A (2016) Intravital 5(1): e1125562
    › Primary publication · 28243517 (PubMed) · PMC5226013 (PubMed Central)
  17. In vivo histone H1 migration from necrotic to viable tissue. Luhrs KA, Pink D, Schulte W, Zijlstra A, Lewis JD, Parseghian MH (2017) Oncotarget 8(10): 16275-16292
    › Primary publication · 28187445 (PubMed) · PMC5369962 (PubMed Central)
  18. Larger core size has superior technical and analytical accuracy in bladder tissue microarray. Eskaros AR, Egloff SA, Boyd KL, Richardson JE, Hyndman ME, Zijlstra A (2017) Lab Invest 97(3): 335-342
    › Primary publication · 28112755 (PubMed)
  19. Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer. Arnold Egloff SA, Du L, Loomans HA, Starchenko A, Su PF, Ketova T, Knoll PB, Wang J, Haddad AQ, Fadare O, Cates JM, Lotan Y, Shyr Y, Clark PE, Zijlstra A (2017) Oncotarget 8(1): 722-741
    › Primary publication · 27894096 (PubMed) · PMC5352192 (PubMed Central)
  20. Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream. Weber MR, Zuka M, Lorger M, Tschan M, Torbett BE, Zijlstra A, Quigley JP, Staflin K, Eliceiri BP, Krueger JS, Marchese P, Ruggeri ZM, Felding BH (2016) Thromb Res : S27-36
    › Primary publication · 27067975 (PubMed) · PMC4888909 (PubMed Central)
  21. High efficacy vasopermeability drug candidates identified by screening in an ex ovo chorioallantoic membrane model. Pink D, Luhrs KA, Zhou L, Schulte W, Chase J, Frosch C, Haberl U, Nguyen V, Roy AI, Lewis JD, Zijlstra A, Parseghian MH (2015) Sci Rep : 15756
    › Primary publication · 26510887 (PubMed) · PMC4625159 (PubMed Central)
  22. Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer. Arnold SA, Loomans HA, Ketova T, Andl CD, Clark PE, Zijlstra A (2016) Clin Exp Metastasis 33(1): 29-44
    › Primary publication · 26456754 (PubMed) · PMC4742427 (PubMed Central)
  23. TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton. Preston Campbell J, Mulcrone P, Masood SK, Karolak M, Merkel A, Hebron K, Zijlstra A, Sterling J, Elefteriou F (2015) Sci Rep : 12635
    › Primary publication · 26271202 (PubMed) · PMC4536516 (PubMed Central)
  24. Small molecule/ML327 mediated transcriptional de-repression of E-cadherin and inhibition of epithelial-to-mesenchymal transition. An H, Stoops SL, Deane NG, Zhu J, Zi J, Weaver C, Waterson AG, Zijlstra A, Lindsley CW, Beauchamp RD (2015) Oncotarget 6(26): 22934-48
    › Primary publication · 26082441 (PubMed) · PMC4673210 (PubMed Central)
  25. Directional cell movement through tissues is controlled by exosome secretion. Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM (2015) Nat Commun : 7164
    › Primary publication · 25968605 (PubMed) · PMC4435734 (PubMed Central)
  26. Intrinsic TGF-β2-triggered SDF-1-CXCR4 signaling axis is crucial for drug resistance and a slow-cycling state in bone marrow-disseminated tumor cells. Nakamura T, Shinriki S, Jono H, Guo J, Ueda M, Hayashi M, Yamashita S, Zijlstra A, Nakayama H, Hiraki A, Shinohara M, Ando Y (2015) Oncotarget 6(2): 1008-19
    › Primary publication · 25504440 (PubMed) · PMC4359213 (PubMed Central)
  27. Metastasis as a therapeutic target in prostate cancer: a conceptual framework. Stoletov K, Bond D, Hebron K, Raha S, Zijlstra A, Lewis JD (2014) Am J Clin Exp Urol 2(1): 45-56
    › Primary publication · 25360439 (PubMed) · PMC4219290 (PubMed Central)
  28. Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer. Jovanović B, Beeler JS, Pickup MW, Chytil A, Gorska AE, Ashby WJ, Lehmann BD, Zijlstra A, Pietenpol JA, Moses HL (2014) Breast Cancer Res 16(4): R69
    › Primary publication · 24985072 (PubMed) · PMC4095685 (PubMed Central)
  29. Techniques and assays for the study of angiogenesis. Irvin MW, Zijlstra A, Wikswo JP, Pozzi A (2014) Exp Biol Med (Maywood) 239(11): 1476-88
    › Primary publication · 24872440 (PubMed) · PMC4216737 (PubMed Central)
  30. Flipping the switch: integrin switching provides metastatic competence. Madamanchi A, Zijlstra A, Zutter MM (2014) Sci Signal 7(318): pe9
    › Primary publication · 24667375 (PubMed) · PMC4209128 (PubMed Central)
  31. ALCAM/CD166 is a TGF-β-responsive marker and functional regulator of prostate cancer metastasis to bone. 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 (2014) Cancer Res 74(5): 1404-15
    › Primary publication · 24385212 (PubMed) · PMC4149913 (PubMed Central)
  32. The chick embryo as an expanding experimental model for cancer and cardiovascular research. Kain KH, Miller JW, Jones-Paris CR, Thomason RT, Lewis JD, Bader DM, Barnett JV, Zijlstra A (2014) Dev Dyn 243(2): 216-28
    › Primary publication · 24357262 (PubMed) · PMC4164046 (PubMed Central)
  33. Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. 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 (2014) Cancer Res 74(1): 173-87
    › Primary publication · 24220242 (PubMed) · PMC3947299 (PubMed Central)
  34. Elevated ALCAM shedding in colorectal cancer correlates with poor patient outcome. Hansen AG, Freeman TJ, Arnold SA, Starchenko A, Jones-Paris CR, Gilger MA, Washington MK, Fan KH, Shyr Y, Beauchamp RD, Zijlstra A (2013) Cancer Res 73(10): 2955-64
    › Primary publication · 23539446 (PubMed) · PMC3660148 (PubMed Central)
  35. Established and novel methods of interrogating two-dimensional cell migration. Ashby WJ, Zijlstra A (2012) Integr Biol (Camb) 4(11): 1338-50
    › Primary publication · 23038152 (PubMed) · PMC4165521 (PubMed Central)
  36. Magnetically attachable stencils and the non-destructive analysis of the contribution made by the underlying matrix to cell migration. Ashby WJ, Wikswo JP, Zijlstra A (2012) Biomaterials 33(33): 8189-203
    › Primary publication · 22940214 (PubMed) · PMC3444626 (PubMed Central)
  37. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice. Campbell JP, Karolak MR, Ma Y, Perrien DS, Masood-Campbell SK, Penner NL, Munoz SA, Zijlstra A, Yang X, Sterling JA, Elefteriou F (2012) PLoS Biol 10(7): e1001363
    › Primary publication · 22815651 (PubMed) · PMC3398959 (PubMed Central)
  38. Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk. Matise LA, Palmer TD, Ashby WJ, Nashabi A, Chytil A, Aakre M, Pickup MW, Gorska AE, Zijlstra A, Moses HL (2012) Breast Cancer Res 14(4): R98
    › Primary publication · 22748014 (PubMed) · PMC3680921 (PubMed Central)
  39. Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery. Pink DB, Schulte W, Parseghian MH, Zijlstra A, Lewis JD (2012) PLoS One 7(3): e33760
    › Primary publication · 22479438 (PubMed) · PMC3315578 (PubMed Central)
  40. Evaluation of nanoparticle uptake in tumors in real time using intravital imaging. Cho CF, Ablack A, Leong HS, Zijlstra A, Lewis J (2011) J Vis Exp (52)
    › Primary publication · 21730939 (PubMed) · PMC3197055 (PubMed Central)
  41. Quantitative analysis of cancer metastasis using an avian embryo model. Palmer TD, Lewis J, Zijlstra A (2011) J Vis Exp (51)
    › Primary publication · 21673636 (PubMed) · PMC3197130 (PubMed Central)
  42. Targeting tumor cell motility to prevent metastasis. Palmer TD, Ashby WJ, Lewis JD, Zijlstra A (2011) Adv Drug Deliv Rev 63(8): 568-81
    › Primary publication · 21664937 (PubMed) · PMC3132821 (PubMed Central)
  43. A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology. Gao Y, Majumdar D, Jovanovic B, Shaifer C, Lin PC, Zijlstra A, Webb DJ, Li D (2011) Biomed Microdevices 13(3): 539-48
    › Primary publication · 21424383 (PubMed) · PMC3085600 (PubMed Central)
  44. The α₂β₁ integrin is a metastasis suppressor in mouse models and human cancer. Ramirez NE, Zhang Z, Madamanchi A, Boyd KL, O'Rear LD, Nashabi A, Li Z, Dupont WD, Zijlstra A, Zutter MM (2011) J Clin Invest 121(1): 226-37
    › Primary publication · 21135504 (PubMed) · PMC3007139 (PubMed Central)
  45. Intravital imaging of embryonic and tumor neovasculature using viral nanoparticles. Leong HS, Steinmetz NF, Ablack A, Destito G, Zijlstra A, Stuhlmann H, Manchester M, Lewis JD (2010) Nat Protoc 5(8): 1406-17
    › Primary publication · 20671724 (PubMed) · PMC3163450 (PubMed Central)
  46. Sensitivity of cancer cells to truncated diphtheria toxin. Zhang Y, Schulte W, Pink D, Phipps K, Zijlstra A, Lewis JD, Waisman DM (2010) PLoS One 5(5): e10498
    › Primary publication · 20463924 (PubMed) · PMC2864767 (PubMed Central)
  47. Launching an academic research career. Zijlstra A (2009) Dis Model Mech 2(11-12): 526-30
    › Primary publication · 19892881 (PubMed)
  48. The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151. Zijlstra A, Lewis J, Degryse B, Stuhlmann H, Quigley JP (2008) Cancer Cell 13(3): 221-34
    › Primary publication · 18328426 (PubMed) · PMC3068919 (PubMed Central)
  49. CD98hc (SLC3A2) participates in fibronectin matrix assembly by mediating integrin signaling. Féral CC, Zijlstra A, Tkachenko E, Prager G, Gardel ML, Slepak M, Ginsberg MH (2007) J Cell Biol 178(4): 701-11
    › Primary publication · 17682053 (PubMed) · PMC2064475 (PubMed Central)
  50. The DARC side of metastasis: shining a light on KAI1-mediated metastasis suppression in the vascular tunnel. Zijlstra A, Quigley JP (2006) Cancer Cell 10(3): 177-8
    › Primary publication · 16959609 (PubMed)
  51. Viral nanoparticles as tools for intravital vascular imaging. Lewis JD, Destito G, Zijlstra A, Gonzalez MJ, Quigley JP, Manchester M, Stuhlmann H (2006) Nat Med 12(3): 354-60
    › Primary publication · 16501571 (PubMed) · PMC2536493 (PubMed Central)
  52. Unexpected effect of matrix metalloproteinase down-regulation on vascular intravasation and metastasis of human fibrosarcoma cells selected in vivo for high rates of dissemination. Deryugina EI, Zijlstra A, Partridge JJ, Kupriyanova TA, Madsen MA, Papagiannakopoulos T, Quigley JP (2005) Cancer Res 65(23): 10959-69
    › Primary publication · 16322244 (PubMed)
  53. Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells. Zijlstra A, Seandel M, Kupriyanova TA, Partridge JJ, Madsen MA, Hahn-Dantona EA, Quigley JP, Deryugina EI (2006) Blood 107(1): 317-27
    › Primary publication · 16174763 (PubMed) · PMC1895349 (PubMed Central)
  54. Genetic reprogramming of tumor cells by zinc finger transcription factors. Blancafort P, Chen EI, Gonzalez B, Bergquist S, Zijlstra A, Guthy D, Brachat A, Brakenhoff RH, Quigley JP, Erdmann D, Barbas CF (2005) Proc Natl Acad Sci U S A 102(33): 11716-21
    › Primary publication · 16081541 (PubMed) · PMC1187960 (PubMed Central)
  55. The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. Wilson S, Greer B, Hooper J, Zijlstra A, Walker B, Quigley J, Hawthorne S (2005) Biochem J 388(Pt 3): 967-72
    › Primary publication · 15537383 (PubMed) · PMC1183478 (PubMed Central)
  56. Collagenolysis-dependent angiogenesis mediated by matrix metalloproteinase-13 (collagenase-3). Zijlstra A, Aimes RT, Zhu D, Regazzoni K, Kupriyanova T, Seandel M, Deryugina EI, Quigley JP (2004) J Biol Chem 279(26): 27633-45
    › Primary publication · 15066996 (PubMed)
  57. Expression and assembly of the angiogenic marker B-fibronectin by endothelial cells in vitro: regulation by confluency. Zijlstra A, McCabe NR, Schelling ME (1999) Angiogenesis 3(1): 77-87
    › Primary publication · 14517447 (PubMed)
  58. Targeting the proteome/epitome, implementation of subtractive immunization. Zijlstra A, Testa JE, Quigley JP (2003) Biochem Biophys Res Commun 303(3): 733-44
    › Primary publication · 12670472 (PubMed)
  59. Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen. Hooper JD, Zijlstra A, Aimes RT, Liang H, Claassen GF, Tarin D, Testa JE, Quigley JP (2003) Oncogene 22(12): 1783-94
    › Primary publication · 12660814 (PubMed)
  60. Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Aimes RT, Zijlstra A, Hooper JD, Ogbourne SM, Sit ML, Fuchs S, Gotley DC, Quigley JP, Antalis TM (2003) Thromb Haemost 89(3): 561-72
    › Primary publication · 12624642 (PubMed)
  61. A quantitative analysis of rate-limiting steps in the metastatic cascade using human-specific real-time polymerase chain reaction. Zijlstra A, Mellor R, Panzarella G, Aimes RT, Hooper JD, Marchenko ND, Quigley JP (2002) Cancer Res 62(23): 7083-92
    › Primary publication · 12460930 (PubMed)
  62. Lack of specificity of endoglin expression for tumor blood vessels. Balza E, Castellani P, Zijlstra A, Neri D, Zardi L, Siri A (2001) Int J Cancer 94(4): 579-85
    › Primary publication · 11745447 (PubMed)
  63. Detection of multiple fibronectin isoforms in fetal fibroblast monolayer culture: a novel method for the qualitative and quantitative detection of multiple antigens. Zijlstra A, Schelling ME (1999) Histochem Cell Biol 111(2): 163-9
    › Primary publication · 10090577 (PubMed)