Barbara Fingleton
Faculty Member
Last active: 4/11/2016

Profile

The overarching theme of the Fingleton lab is tumor microenvironmental interactions, in the settings of breast and colon cancer. Within this general framework, we have two main areas of focus: (i) matrix metalloproteinases and their roles in inflammation and in metastasis; and (ii) the Th2 cytokines IL4 and IL13 and their functions in epithelial tumor cells. Our interest in matrix metalloproteinases (MMPs) is long-standing and incorporates collaborative studies with ex vivo and in vivo imaging of proteolytic activity using probes developed in-house. These studies are facilitated by the expertise in imaging and state-of-the art instrumentation available at Vanderbilt. Additionally, we use a range of genetically manipulated mouse models combined with cell culture experiments to identify and characterize specific functions of different members of the MMP family in all stages of tumor progression. These studies are then validated using clinical samples to ensure relevance to patients. We have also collaborated with several pharmaceutical and biotechnology companies to test broad-spectrum as well as specific antibody-based inhibitors of MMPs in cancer as well as inflammatory models. Current areas of interest are determining whether a specific MMP (MMP10) is necessary for the tumor-associated macrophage phenotype, and how macrophage activity in colitis could influence future tumor development. The other main area of focus – epithelial functions of IL4 and IL13 – is also pursued using a combination of genetically manipulated mouse models, cell culture and novel protein therapeutics provided through industry collaborations. We have established that signaling through the IL4 receptor on epithelial cells promotes metastatic survival in colon and breast cancer.. We are also working on delineating differential functions of the two cytokine ligands IL13 and IL4, and their respective contributions to chemoresistance in advanced colon cancer.

Publications

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

Featured publications are shown below:

  1. Targeting IL4/IL4R for the treatment of epithelial cancer metastasis. Bankaitis KV, Fingleton B (2015) Clin Exp Metastasis 32(8): 847-56
    › Primary publication · 26385103 (PubMed) · PMC4651701 (PubMed Central)
  2. Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage. Barrett CW, Reddy VK, Short SP, Motley AK, Lintel MK, Bradley AM, Freeman T, Vallance J, Ning W, Parang B, Poindexter SV, Fingleton B, Chen X, Washington MK, Wilson KT, Shroyer NF, Hill KE, Burk RF, Williams CS (2015) J Clin Invest 125(7): 2646-60
    › Primary publication · 26053663 (PubMed) · PMC4563672 (PubMed Central)
  3. Lessons from immunology: IL4R directly promotes mammary tumor metastasis. Venmar KT, Fingleton B (2014) Oncoimmunology 3(9): e955373
    › Primary publication · 25941616 (PubMed) · PMC4292563 (PubMed Central)
  4. Host and tumor derived MMP13 regulate extravasation and establishment of colorectal metastases in the liver. Mendonsa AM, VanSaun MN, Ustione A, Piston DW, Fingleton BM, Gorden DL (2015) Mol Cancer : 49
    › Primary publication · 25880591 (PubMed) · PMC4351934 (PubMed Central)
  5. IL4 receptor α mediates enhanced glucose and glutamine metabolism to support breast cancer growth. Venmar KT, Kimmel DW, Cliffel DE, Fingleton B (2015) Biochim Biophys Acta 1853(5): 1219-28
    › Primary publication · 25746764 (PubMed) · PMC4380623 (PubMed Central)
  6. Moving targets: Emerging roles for MMPs in cancer progression and metastasis. Shay G, Lynch CC, Fingleton B (2015) Matrix Biol : 200-6
    › Primary publication · 25652204 (PubMed) · PMC4564058 (PubMed Central)
  7. Stromal matrix metalloproteinase 2 regulates collagen expression and promotes the outgrowth of experimental metastases. Bates AL, Pickup MW, Hallett MA, Dozier EA, Thomas S, Fingleton B (2015) J Pathol 235(5): 773-83
    › Primary publication · 25469981 (PubMed) · PMC4357558 (PubMed Central)
  8. IL4 receptor ILR4α regulates metastatic colonization by mammary tumors through multiple signaling pathways. Venmar KT, Carter KJ, Hwang DG, Dozier EA, Fingleton B (2014) Cancer Res 74(16): 4329-40
    › Primary publication · 24947041 (PubMed) · PMC4134711 (PubMed Central)
  9. Macrophages promote progression of spasmolytic polypeptide-expressing metaplasia after acute loss of parietal cells. Petersen CP, Weis VG, Nam KT, Sousa JF, Fingleton B, Goldenring JR (2014) Gastroenterology 146(7): 1727-38.e8
    › Primary publication · 24534633 (PubMed) · PMC4035414 (PubMed Central)
  10. Systems-level analysis of proteolytic events in increased vascular permeability and complement activation in skin inflammation. auf dem Keller U, Prudova A, Eckhard U, Fingleton B, Overall CM (2013) Sci Signal 6(258): rs2
    › Primary publication · 23322905 (PubMed) · PMC3872078 (PubMed Central)
  11. Cytokine stimulation of epithelial cancer cells: the similar and divergent functions of IL-4 and IL-13. Hallett MA, Venmar KT, Fingleton B (2012) Cancer Res 72(24): 6338-43
    › Primary publication · 23222300 (PubMed) · PMC3531868 (PubMed Central)
  12. Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia. Koller FL, Dozier EA, Nam KT, Swee M, Birkland TP, Parks WC, Fingleton B (2012) Lab Invest 92(12): 1749-59
    › Primary publication · 23044923 (PubMed) · PMC3510327 (PubMed Central)
  13. Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA. Lynch CC, Vargo-Gogola T, Matrisian LM, Fingleton B (2010) J Oncol : 530745
    › Primary publication · 20628524 (PubMed) · PMC2902104 (PubMed Central)
  14. Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion. Stathopoulos GT, Sherrill TP, Karabela SP, Goleniewska K, Kalomenidis I, Roussos C, Fingleton B, Yull FE, Peebles RS, Blackwell TS (2010) Am J Respir Crit Care Med 182(10): 1273-81
    › Primary publication · 20595227 (PubMed) · PMC3001265 (PubMed Central)
  15. Epithelial interleukin-4 receptor expression promotes colon tumor growth. Koller FL, Hwang DG, Dozier EA, Fingleton B (2010) Carcinogenesis 31(6): 1010-7
    › Primary publication · 20176658 (PubMed) · PMC2878360 (PubMed Central)
  16. A new dress code for MMPs: cleavage optional. Fingleton B, Lynch CC (2010) Dev Cell 18(1): 3-4
    › Primary publication · 20152171 (PubMed)
  17. Inflammatory proteinase slips into tumor cells. Fingleton B (2010) Nat Med 16(2): 161-3
    › Primary publication · 20134467 (PubMed)
  18. Matrix metalloproteinase-7 and premalignant host responses in Helicobacter pylori-infected mice. Ogden SR, Noto JM, Allen SS, Patel DA, Romero-Gallo J, Washington MK, Fingleton B, Israel DA, Lewis ND, Wilson KT, Chaturvedi R, Zhao Z, Shyr Y, Peek RM (2010) Cancer Res 70(1): 30-5
    › Primary publication · 20048070 (PubMed) · PMC2804939 (PubMed Central)
  19. Matrix metalloproteinase-9 contributes to intestinal tumourigenesis in the adenomatous polyposis coli multiple intestinal neoplasia mouse. Sinnamon MJ, Carter KJ, Fingleton B, Matrisian LM (2008) Int J Exp Pathol 89(6): 466-75
    › Primary publication · 19134056 (PubMed) · PMC2669608 (PubMed Central)
  20. Establishment and quantitative imaging of a 3D lung organotypic model of mammary tumor outgrowth. Martin MD, Fingleton B, Lynch CC, Wells S, McIntyre JO, Piston DW, Matrisian LM (2008) Clin Exp Metastasis 25(8): 877-85
    › Primary publication · 18787962 (PubMed) · PMC2588650 (PubMed Central)
  21. Functional colonography of Min mice using dark lumen dynamic contrast-enhanced MRI. Quarles CC, Lepage M, Gorden DL, Fingleton B, Yankeelov TE, Price RR, Matrisian LM, Gore JC, McIntyre JO (2008) Magn Reson Med 60(3): 718-26
    › Primary publication · 18727087 (PubMed) · PMC2646120 (PubMed Central)
  22. Effect of ablation or inhibition of stromal matrix metalloproteinase-9 on lung metastasis in a breast cancer model is dependent on genetic background. Martin MD, Carter KJ, Jean-Philippe SR, Chang M, Mobashery S, Thiolloy S, Lynch CC, Matrisian LM, Fingleton B (2008) Cancer Res 68(15): 6251-9
    › Primary publication · 18676849 (PubMed) · PMC2789265 (PubMed Central)
  23. p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7. Ogden SR, Wroblewski LE, Weydig C, Romero-Gallo J, O'Brien DP, Israel DA, Krishna US, Fingleton B, Reynolds AB, Wessler S, Peek RM (2008) Mol Biol Cell 19(10): 4110-21
    › Primary publication · 18653469 (PubMed) · PMC2555941 (PubMed Central)
  24. Host nuclear factor-kappaB activation potentiates lung cancer metastasis. Stathopoulos GT, Sherrill TP, Han W, Sadikot RT, Yull FE, Blackwell TS, Fingleton B (2008) Mol Cancer Res 6(3): 364-71
    › Primary publication · 18337446 (PubMed)
  25. A protective role of mast cells in intestinal tumorigenesis. Sinnamon MJ, Carter KJ, Sims LP, Lafleur B, Fingleton B, Matrisian LM (2008) Carcinogenesis 29(4): 880-6
    › Primary publication · 18258601 (PubMed)
  26. Noninvasive detection of matrix metalloproteinase activity in vivo using a novel magnetic resonance imaging contrast agent with a solubility switch. Lepage M, Dow WC, Melchior M, You Y, Fingleton B, Quarles CC, Pépin C, Gore JC, Matrisian LM, McIntyre JO (2007) Mol Imaging 6(6): 393-403
    › Primary publication · 18053410 (PubMed)
  27. Use of bioluminescent imaging to investigate the role of nuclear factor-kappaBeta in experimental non-small cell lung cancer metastasis. Stathopoulos GT, Sherrill TP, Han W, Sadikot RT, Polosukhin VV, Fingleton B, Yull FE, Blackwell TS (2008) Clin Exp Metastasis 25(1): 43-51
    › Primary publication · 18008176 (PubMed)
  28. Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Stathopoulos GT, Sherrill TP, Cheng DS, Scoggins RM, Han W, Polosukhin VV, Connelly L, Yull FE, Fingleton B, Blackwell TS (2007) Proc Natl Acad Sci U S A 104(47): 18514-9
    › Primary publication · 18000061 (PubMed) · PMC2141808 (PubMed Central)
  29. Molecular targets in metastasis: lessons from genomic approaches. Fingleton B (2007) Cancer Genomics Proteomics 4(3): 211-21
    › Primary publication · 17878524 (PubMed)
  30. MMPs as therapeutic targets--still a viable option? Fingleton B (2008) Semin Cell Dev Biol 19(1): 61-8
    › Primary publication · 17693104 (PubMed) · PMC2677300 (PubMed Central)
  31. Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor. Lynch CC, Vargo-Gogola T, Martin MD, Fingleton B, Crawford HC, Matrisian LM (2007) Cancer Res 67(14): 6760-7
    › Primary publication · 17638887 (PubMed)
  32. Loss of functional Fas ligand enhances intestinal tumorigenesis in the Min mouse model. Fingleton B, Carter KJ, Matrisian LM (2007) Cancer Res 67(10): 4800-6
    › Primary publication · 17510409 (PubMed)
  33. Hu/Mu ProtIn oligonucleotide microarray: dual-species array for profiling protease and protease inhibitor gene expression in tumors and their microenvironment. Schwartz DR, Moin K, Yao B, Matrisian LM, Coussens LM, Bugge TH, Fingleton B, Acuff HB, Sinnamon M, Nassar H, Platts AE, Krawetz SA, Linebaugh BE, Sloane BF (2007) Mol Cancer Res 5(5): 443-54
    › Primary publication · 17510311 (PubMed)
  34. Resident stromal cell-derived MMP-9 promotes the growth of colorectal metastases in the liver microenvironment. Gorden DL, Fingleton B, Crawford HC, Jansen DE, Lepage M, Matrisian LM (2007) Int J Cancer 121(3): 495-500
    › Primary publication · 17417772 (PubMed)
  35. A rat monoclonal antibody that recognizes pro- and active MMP-7 indicates polarized expression in vivo. Fingleton B, Powell WC, Crawford HC, Couchman JR, Matrisian LM (2007) Hybridoma (Larchmt) 26(1): 22-7
    › Primary publication · 17316082 (PubMed) · PMC3838102 (PubMed Central)
  36. Matrix metalloproteinases as valid clinical targets. Fingleton B (2007) Curr Pharm Des 13(3): 333-46
    › Primary publication · 17313364 (PubMed)
  37. Analysis of host- and tumor-derived proteinases using a custom dual species microarray reveals a protective role for stromal matrix metalloproteinase-12 in non-small cell lung cancer. Acuff HB, Sinnamon M, Fingleton B, Boone B, Levy SE, Chen X, Pozzi A, Carbone DP, Schwartz DR, Moin K, Sloane BF, Matrisian LM (2006) Cancer Res 66(16): 7968-75
    › Primary publication · 16912171 (PubMed)
  38. Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment. Acuff HB, Carter KJ, Fingleton B, Gorden DL, Matrisian LM (2006) Cancer Res 66(1): 259-66
    › Primary publication · 16397239 (PubMed) · PMC1360653 (PubMed Central)
  39. Matrix metalloproteinases: roles in cancer and metastasis. Fingleton B (2006) Front Biosci : 479-91
    › Primary publication · 16146745 (PubMed)
  40. An orthotopic model of lung cancer to analyze primary and metastatic NSCLC growth in integrin alpha1-null mice. Chen X, Su Y, Fingleton B, Acuff H, Matrisian LM, Zent R, Pozzi A (2005) Clin Exp Metastasis 22(2): 185-93
    › Primary publication · 16086239 (PubMed)
  41. MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Lynch CC, Hikosaka A, Acuff HB, Martin MD, Kawai N, Singh RK, Vargo-Gogola TC, Begtrup JL, Peterson TE, Fingleton B, Shirai T, Matrisian LM, Futakuchi M (2005) Cancer Cell 7(5): 485-96
    › Primary publication · 15894268 (PubMed)
  42. Increased plasma MMP9 in integrin alpha1-null mice enhances lung metastasis of colon carcinoma cells. Chen X, Su Y, Fingleton B, Acuff H, Matrisian LM, Zent R, Pozzi A (2005) Int J Cancer 116(1): 52-61
    › Primary publication · 15756690 (PubMed)
  43. Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells. Harrell PC, McCawley LJ, Fingleton B, McIntyre JO, Matrisian LM (2005) Exp Cell Res 303(2): 308-20
    › Primary publication · 15652345 (PubMed)
  44. Proteinase activity in human and murine saliva as a biomarker for proteinase inhibitor efficacy. Fingleton B, Menon R, Carter KJ, Overstreet PD, Hachey DL, Matrisian LM, McIntyre JO (2004) Clin Cancer Res 10(23): 7865-74
    › Primary publication · 15585619 (PubMed)
  45. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y, Matrisian LM, Carbone DP, Lin PC (2004) Cancer Cell 6(4): 409-21
    › Primary publication · 15488763 (PubMed)
  46. Tcf binding sequence and position determines beta-catenin and Lef-1 responsiveness of MMP-7 promoters. Gustavson MD, Crawford HC, Fingleton B, Matrisian LM (2004) Mol Carcinog 41(3): 125-39
    › Primary publication · 15457508 (PubMed)
  47. Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration. Mohammed FF, Smookler DS, Taylor SE, Fingleton B, Kassiri Z, Sanchez OH, English JL, Matrisian LM, Au B, Yeh WC, Khokha R (2004) Nat Genet 36(9): 969-77
    › Primary publication · 15322543 (PubMed)
  48. The influence of matrix metalloproteinase-7 on early mammary tumorigenesis in the multiple intestinal neoplasia mouse. Hulboy DL, Gautam S, Fingleton B, Matrisian LM (2004) Oncol Rep 12(1): 13-7
    › Primary publication · 15201952 (PubMed)
  49. CMT-3. CollaGenex. Fingleton B (2003) Curr Opin Investig Drugs 4(12): 1460-7
    › Primary publication · 14763133 (PubMed)
  50. Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. McIntyre JO, Fingleton B, Wells KS, Piston DW, Lynch CC, Gautam S, Matrisian LM (2004) Biochem J 377(Pt 3): 617-28
    › Primary publication · 14556651 (PubMed) · PMC1223892 (PubMed Central)
  51. Matrix metalloproteinase inhibitors for cancer therapy:the current situation and future prospects. Fingleton B (2003) Expert Opin Ther Targets 7(3): 385-97
    › Primary publication · 12783574 (PubMed)
  52. Identification of novel matrix metalloproteinase-7 (matrilysin) cleavage sites in murine and human Fas ligand. Vargo-Gogola T, Crawford HC, Fingleton B, Matrisian LM (2002) Arch Biochem Biophys 408(2): 155-61
    › Primary publication · 12464266 (PubMed)
  53. Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo. Vargo-Gogola T, Fingleton B, Crawford HC, Matrisian LM (2002) Cancer Res 62(19): 5559-63
    › Primary publication · 12359768 (PubMed)
  54. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Coussens LM, Fingleton B, Matrisian LM (2002) Science 295(5564): 2387-92
    › Primary publication · 11923519 (PubMed)
  55. Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Fingleton B, Vargo-Gogola T, Crawford HC, Matrisian LM (2001) Neoplasia 3(6): 459-68
    › Primary publication · 11774028 (PubMed) · PMC1506562 (PubMed Central)
  56. Matrix metalloproteinases as targets for therapy in Kaposi sarcoma. Fingleton B, Matrisian LM (2001) Curr Opin Oncol 13(5): 368-73
    › Primary publication · 11555714 (PubMed)
  57. The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Crawford HC, Fingleton B, Gustavson MD, Kurpios N, Wagenaar RA, Hassell JA, Matrisian LM (2001) Mol Cell Biol 21(4): 1370-83
    › Primary publication · 11158322 (PubMed) · PMC99589 (PubMed Central)
  58. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. Noë V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM, Mareel M (2001) J Cell Sci 114(Pt 1): 111-118
    › Primary publication · 11112695 (PubMed)
  59. Matrix metalloproteinases: biologic activity and clinical implications. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM (2000) J Clin Oncol 18(5): 1135-49
    › Primary publication · 10694567 (PubMed)
  60. Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption. Haro H, Crawford HC, Fingleton B, Shinomiya K, Spengler DM, Matrisian LM (2000) J Clin Invest 105(2): 143-50
    › Primary publication · 10642592 (PubMed) · PMC377426 (PubMed Central)
  61. Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption. Haro H, Crawford HC, Fingleton B, MacDougall JR, Shinomiya K, Spengler DM, Matrisian LM (2000) J Clin Invest 105(2): 133-41
    › Primary publication · 10642591 (PubMed) · PMC377425 (PubMed Central)
  62. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Powell WC, Fingleton B, Wilson CL, Boothby M, Matrisian LM (1999) Curr Biol 9(24): 1441-7
    › Primary publication · 10607586 (PubMed)
  63. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Crawford HC, Fingleton BM, Rudolph-Owen LA, Goss KJ, Rubinfeld B, Polakis P, Matrisian LM (1999) Oncogene 18(18): 2883-91
    › Primary publication · 10362259 (PubMed)
  64. Matrilysin in early stage intestinal tumorigenesis. Fingleton BM, Heppner Goss KJ, Crawford HC, Matrisian LM (1999) APMIS 107(1): 102-10
    › Primary publication · 10190286 (PubMed)
  65. Cytokine regulation of matrilysin gene expression. Fingleton B, McDonnell S (1997) Biochem Soc Trans 25(2): 155S
    › Primary publication · 9191199 (PubMed)
  66. Role of matrix metalloproteinases in invasion and metastasis: biology, diagnosis and inhibitors. McDonnell S, Fingleton B (1993) Cytotechnology 12(1-3): 367-84
    › Primary publication · 7764458 (PubMed)