Photo of Bruce R. Zetter,  PhD

Bruce R. Zetter, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2320
Fax: (617) 730-0268

Bruce R. Zetter, PhD

Boston Children's Hospital


  • Charles Nowiszewski Professor of Cancer Biology, Surgery, Harvard Medical School


Research Abstract

Our research is focused on the changes in gene and protein expression that take place as tumors progress from highly differentiated, non-aggressive lesions to poorly differentiated, metastatic tumors. The phenotype required for metastasis includes decreased cell aggregation, increased angiogenesis, increased cell migration and increased tissue degradation. The goal of our laboratory is to identify these molecules, to determine the mechanism by which their expression is altered in tumor progression and to employ them for both diagnostic and therapeutic purposes.

Using proteomics tools, we have identified a variety of proteins altered in tumor progression in breast, pancreas, prostate, bladder and other tumor sites. Our model systems include tumor cell lines that differ in their metastatic potential, as well as transgenic animal models in which tumors arise spontaneously in the prostate or pancreas at distinct times after birth. Using this approach, we have developed tests for biomarkers that are useful in cancer diagnosis, prognosis, recurrence monitoring and in determining responsiveness to particular therapeutic agents.

We have recently focused on the development of resistance to taxanes. Taxanes such as paclitaxel and docetaxel are now front-line treatment for patients with a variety of metastatic cancers, yet their efficacy is diminished by the rapid development of drug resistance. We have found that the protein Prohibitin1 is upregulated on the surface of taxane-resistant cells. We believe that Prohibitin1 can be used as a biomarker to reveal which patients have tumors that will be resistant to taxane treatment. In addition, cell surface Prohibitin1 could serve as a target to direct other drugs to taxane-resistant tumor cells.

Because metastasis is the end point for most human cancers and because metastatic lesions are so often resistant to conventional therapies, we have initiated a drug screen to identify new therapies that act preferentially on metastatic tumors. We have identified several candidate therapies that we now wish to move rapidly to clinical trial.


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  • Zhu X, Xu Y, Solis LM, Tao W, Wang L, Behrens C, Xu X, Zhao L, Liu D, Wu J, Zhang N, Wistuba II, Farokhzad OC, Zetter BR, Shi J. Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment. Proc Natl Acad Sci U S A 2015; 112:7779-84. PubMed
  • Shi J, Xu Y, Xu X, Zhu X, Pridgen E, Wu J, Votruba AR, Archana S, Zetter BR, Farokhzad OC. Hybrid lipid-polymer nanoparticles for sustained siRNA delivery and gene silencing. 2014. PubMed
  • Banyard J, Chung I, Migliozzi M, Phan DT, Wilson AM, Zetter BR, Bielenberg DR. Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer. BMC Cancer 2014; 14:387. PubMed
  • Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, Stanger BZ, Chung I, Rhim AD, di Magliano MP. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res 2013; 73:6359-74. PubMed
  • Banyard J, Chung I, Wilson AM, Vetter G, Le Béchec A, Bielenberg DR, Zetter BR. Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model. Sci Rep 2013; 3:3151. PubMed
  • Coughlin MF, Bielenberg DR, Lenormand G, Marinkovic M, Waghorne CG, Zetter BR, Fredberg JJ. Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin Exp Metastasis 2012. PubMed
  • Freeman KW, Bowman BR, Zetter BR. Regenerative protein thymosin beta-4 is a novel regulator of purinergic signaling. FASEB J 2011; 25:907-15. PubMed
  • Yang W, Cai Q, Lui VW, Everley PA, Kim J, Bhola N, Quesnelle KM, Zetter BR, Steen H, Freeman MR, Grandis JR. Quantitative Proteomics Analysis Reveals Molecular Networks Regulated by Epidermal Growth Factor Receptor Level in Head and Neck Cancer. J Proteome Res 2010; 9:3073-82. PubMed
  • Spivey KA, Banyard J, Solis LM, Wistuba II, Barletta JA, Gandhi L, Feldman HA, Rodig SJ, Chirieac LR, Zetter BR. Collagen XXIII: a potential biomarker for the detection of primary and recurrent non-small cell lung cancer. Cancer Epidemiol Biomarkers Prev 2010; 19:1362-72. PubMed
  • Mu CJ, Lavan DA, Langer RS, Zetter BR. Self-Assembled Gold Nanoparticle Molecular Probes for Detecting Proteolytic Activity In Vivo. ACS Nano 2010; 4:1511-20. PubMed
  • Patel N, Chatterjee SK, Vrbanac V, Chung I, Mu CJ, Olsen RR, Waghorne C, Zetter BR. Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells. Proc Natl Acad Sci U S A 2010; 107:2503-8. PubMed
  • Banyard J,Barrows C,Zetter BR. Differential regulation of human thymosin beta 15 isoforms by transforming growth factor beta 1. Genes Chromosomes Cancer 2009; 48:502-9. PubMed
  • Feldman AS,Banyard J,Wu CL,McDougal WS,Zetter BR. Cystatin B as a tissue and urinary biomarker of bladder cancer recurrence and disease progression. Clin Cancer Res 2009; 15:1024-31. PubMed
  • Zetter BR. The scientific contributions of M. Judah Folkman to cancer research. Nat Rev Cancer 2008; 8:647-54. PubMed
  • Arap W, Trepel M, Zetter BR, Pasqualini R. Meeting report: innovations in prostate cancer research. Cancer Res 2008; 68:635-8. PubMed
  • Mangold U, Hayakawa H, Coughlin M, M. Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification. Oncogene 2007; 27:604-13. PubMed
  • Banyard J, Bao L, Hofer MD, Zurakowski D, Spivey KA, Feldman AS, Hutchinson LM, Kuefer R, Rubin MA, Zetter BR. Collagen XXIII Expression Is Associated with Prostate Cancer Recurrence and Distant Metastases. Clin Cancer Res 2007; 13:2634-42. PubMed
  • Everley PA, Bakalarski CE, Elias JE, Waghorne CG, Beausoleil SA, Gerber SA, Faherty BK, Zetter BR, Gygi SP. Enhanced analysis of metastatic prostate cancer using stable isotopes and high mass accuracy instrumentation. J Proteome Res 2006; 5:1224-31. PubMed
  • Hutchinson LM, Chang EL, Becker CM, Shih MC, Brice M, DeWolf WC, Gaston SM, Zetter BR. Use of thymosin beta15 as a urinary biomarker in human prostate cancer. Prostate 2005; 64:116-27. PubMed
  • Hutchinson LM, Chang EL, Becker CM, Ushiyama N, Behonick D, Shih MC, DeWolf WC, Gaston SM, Zetter BR. Development of a sensitive and specific enzyme-linked immunosorbent assay for thymosin beta15, a urinary biomarker of human prostate cancer. Clin Biochem 2005; 38:558-71. PubMed
  • Chatterjee SK, Zetter BR. Cancer biomarkers: knowing the present and predicting the future. Future Oncol 2006; 1:37-50. PubMed
  • Lader AS, Ramoni MF, Zetter BR, Kohane IS, Kwiatkowski DJ. Identification of a Transcriptional Profile Associated with In Vitro Invasion in Non-Small Cell Lung Cancer Cell Lines. Cancer Biol Ther 2004; 3:624-31. PubMed
  • Banyard J, Bao L, Zetter BR. Type XXIII collagen, a new transmembrane collagen identified in metastatic tumor cells. J Biol Chem 2003; 278:20989-94. PubMed
  • Iordanescu I, Becker C, Zetter B, Dunning P, Taylor GA. Tumor vascularity: evaluation in a murine model with contrast-enhanced color Doppler US effect of angiogenesis inhibitors. Radiology 2002; 222:460-7. PubMed
  • Mangold U, Hayakawa H, Coughlin M, Münger K, Zetter BR. Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification. Oncogene 2008; 27:604-13.
  • Bao L, Loda M, Zetter BR. Thymosin beta15 expression in tumor cell lines with varying metastatic potential. Clin Exp Metastasis 1998; 16:227-33. PubMed
  • Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med 1998; 49:407-24. PubMed
  • Anand-Apte B, Zetter BR, Viswanathan A, Qiu RG, Chen J, Ruggieri R, Symons M. Platelet-derived growth factor and fibronectin-stimulated migration are differentially regulated by the Rac and extracellular signal-regulated kinase pathways. J Biol Chem 1998; 272:30688-92. PubMed
  • Zetter BR. On target with tumor blood vessel markers. Nat Biotechnol 1997; 15:1243-4. PubMed
  • Gold JS, Bao L, Ghoussoub RA, Zetter BR, Rimm DL. Localization and quantitation of expression of the cell motility-related protein thymosin beta15 in human breast tissue. Mod Pathol 1997; 10:1106-12. PubMed
  • Blatch GL, L. Isolation of a mouse cDNA encoding mSTI1, a stress-inducible protein containing the TPR motif. Gene 1997; 194:277-82. PubMed
  • L. Stress-inducible, murine protein mSTI1. Characterization of binding domains for heat shock proteins and in vitro phosphorylation by different kinases. J Biol Chem 1997; 272:1876-84. PubMed
  • Yoshida A, Anand-Apte B, Zetter BR. Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor. Growth Factors 1996; 13:57-64. PubMed
  • Kantor JD, Zetter BR. Cell motility in breast cancer. Cancer Treat Res 1996; 83:303-23. PubMed
  • Smith RC, Litwin MS, Lu Y, Zetter BR. Identification of an endogenous inhibitor of prostatic carcinoma cell growth. Nat Med 1995; 1:1040-5. PubMed
  • Kundra V, Anand-Apte B, Feig LA, Zetter BR. The chemotactic response to PDGF-BB: evidence of a role for Ras. J Cell Biol 1995; 130:725-31. PubMed
  • Brightman SE, Blatch GL, Zetter BR. Isolation of a mouse cDNA encoding MTJ1, a new murine member of the DnaJ family of proteins. Gene 1995; 153:249-54. PubMed
  • Meininger CJ, Brightman SE, Kelly KA, Zetter BR. Increased stem cell factor release by hemangioma-derived endothelial cells. Lab Invest 1995; 72:166-73. PubMed
  • Kundra V, Soker S, Zetter BR. Excess early signaling activity inhibits cellular chemotaxis toward PDGF-BB. Oncogene 1994; 9:1429-35. PubMed
  • Kundra V, Escobedo JA, Kazlauskas A, Kim HK, Rhee SG, Williams LT, Zetter BR. Regulation of chemotaxis by the platelet-derived growth factor receptor-beta. Nature 1994; 367:474-6. PubMed
  • Yenush L, Kundra V, White MF, Zetter BR. Functional domains of the insulin receptor responsible for chemotactic signaling. J Biol Chem 1994; 269:100-4. PubMed
  • Zetter BR. Adhesion molecules in tumor metastasis. Semin Cancer Biol 1993; 4:219-29. PubMed
  • Blood CH, Zetter BR. Laminin regulates a tumor cell chemotaxis receptor through the laminin-binding integrin subunit alpha 6. Cancer Res 1993; 53:2661-6. PubMed
  • Rossi MC, Zetter BR. Selective stimulation of prostatic carcinoma cell proliferation by transferrin. Proc Natl Acad Sci U S A 1992; 89:6197-201. PubMed
  • Meininger CJ, Zetter BR. Mast cells and angiogenesis. Semin Cancer Biol 1992; 3:73-9. PubMed
  • Meininger CJ, Yano H, Rottapel R, Bernstein A, Zsebo KM, Zetter BR. The c-kit receptor ligand functions as a mast cell chemoattractant. Blood 1992; 79:958-63. PubMed
  • Chan BM, Matsuura N, Takada Y, Zetter BR, Hemler ME. In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science 1991; 251:1600-2. PubMed
  • Zetter BR, Brightman SE. Cell motility and the extracellular matrix. Curr Opin Cell Biol 1990; 2:850-6. PubMed
  • Zetter BR. The cellular basis of site-specific tumor metastasis. N Engl J Med 1990; 322:605-12. PubMed
  • Chackal-Roy M, Niemeyer C, Moore M, Zetter BR. Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. J Clin Invest 1989; 84:43-50. PubMed
  • Blood CH, Zetter BR. Membrane-bound protein kinase C modulates receptor affinity and chemotactic responsiveness of Lewis lung carcinoma sublines to an elastin-derived peptide. J Biol Chem 1989; 264:10614-20. PubMed
  • Zetter BR. Assay of capillary endothelial cell migration. Methods Enzymol 1986; 147:135-44. PubMed
  • Netland PA, Zetter BR. Metastatic potential of B16 melanoma cells after in vitro selection for organ-specific adherence. J Cell Biol 1985; 101:720-4. PubMed
  • Zetter BR, Rasmussen N, Brown L. An in vivo assay for chemoattractant activity. Lab Invest 1985; 53:362-8. PubMed
  • Voyta JC, Via DP, Butterfield CE, Zetter BR. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol 1984; 99:2034-40. PubMed
  • Netland PA, Zetter BR. Organ-specific adhesion of metastatic tumor cells in vitro. Science 1984; 224:1113-5. PubMed
  • Chodak GW, Scheiner CJ, Zetter BR. Urine from patients with transitional-cell carcinoma stimulates migration of capillary endothelial cells. N Engl J Med 1981; 305:869-74. PubMed
  • Coughlin SR, Moskowitz MA, Zetter BR, Antoniades HN, Levine L. Platelet-dependent stimulation of prostacyclin synthesis by platelet-derived growth factor. Nature 1980; 288:600-2. PubMed
  • Brouty-Boyé D, Zetter BR. Inhibition of cell motility by interferon. Science 1980; 208:516-8. PubMed
  • Zetter BR. Migration of capillary endothelial cells is stimulated by tumour-derived factors. Nature 1980; 285:41-3. PubMed