Barbara Fingleton, Ph.D.
Assistant Professor of Cancer Biology
Vanderbilt-Ingram Cancer Center
734 Preston Building
Nashvill, TN 37232-6840
The overarching theme of my laboratory is delineating the positive and negative roles of molecules that are typically considered immune-associated, in solid tumors. In particular, we focus on colorectal and breast cancers and the process of metastasis. Despite excellent recovery rates for patients with locally confined cancers, once there is metastatic disease, survival rates are reduced dramatically.
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The overarching theme of my laboratory is delineating the positive and negative roles of molecules that are typically considered immune-associated, in solid tumors. In particular, we focus on colorectal and breast cancers and the process of metastasis. Despite excellent recovery rates for patients with locally confined cancers, once there is metastatic disease, survival rates are reduced dramatically. We want to understand what makes cancers spread where, and when they do?; how do cancerous cells survive in different tissue environments such as lung or liver?; and, most critically, how can we find and treat metastatic disease? We are interested in two particular classes of inflammation-associated molecules as molecular determinants of metastasis: matrix metalloproteinases (MMPs) and interleukins.
- B. Sc., Dublin City University, 1992
- Ph.D., Dublin City University, 1996
- Postdoctoral Fellow, Vanderbilt University, 2001
Understanding function and how to therapeutically target inflammatory molecules in colitis and colon cancer
My background is in the area of matrix metalloproteinases (MMPs) and how they contribute to cancer development and progression. I have been especially interested in testing drugs that can inhibit MMPs in cancer models and in understanding why such drugs have not been effective in human cancer patients. Lately, I have focused on some of the roles of specific MMPs in pre-cancerous inflammatory conditions, particularly colitis. We have identified a protective function for a specific MMP in colitis and are currently working on elucidating the mechanism. Additionally, I work on the cytokines IL4 and IL13 and their receptors ,and how these molecules can influence colon cancer development and progression. We use multiple mouse models combined with in vitro approaches to address the pleiotropic functions of these cytokines which affect both the epithelial cancer cells and the inflammatory infiltrate within tumors.
- Barrett, CW, Fingleton, B, Williams, A, Ning, W, Fischer, MA, Washington, MK, Chaturvedi, R, Wilson, KT, Hiebert, SW, Williams, CS MTGR1 is required for tumorigenesis in the murine AOM/DSS colitis-associated carcinoma model. Cancer Res, 71(4), 1302-12, 2011.
- Koon, HB, Fingleton, B, Lee, JY, Geyer, JT, Cesarman, E, Parise, RA, Egorin, MJ, Dezube, BJ, Aboulafia, D, Krown, SE Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related Kaposi sarcoma. J Acquir Immune Defic Syndr, 56(1), 64-8, 2011.
- Fingleton, B, Lynch, CC A new dress code for MMPs: cleavage optional. Dev Cell, 18(1), 3-4, 2010.
- Lynch, CC, Vargo-Gogola, T, Matrisian, LM, Fingleton, B Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA. J Oncol, 2010530745, 2010.
- Koller, FL, Hwang, DG, Dozier, EA, Fingleton, B Epithelial interleukin-4 receptor expression promotes colon tumor growth. Carcinogenesis, 31(6), 1010-7, 2010.
- Stathopoulos, GT, Sherrill, TP, Karabela, SP, Goleniewska, K, Kalomenidis, I, Roussos, C, Fingleton, B, Yull, FE, Peebles, RS, Blackwell, TS Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion. Am J Respir Crit Care Med, 182(10), 1273-81, 2010.
- Fingleton, B Inflammatory proteinase slips into tumor cells. Nat Med, 16(2), 161-3, 2010.
- 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 Matrix metalloproteinase-7 and premalignant host responses in Helicobacter pylori-infected mice. Cancer Res, 70(1), 30-5, 2010.
- Sinnamon, MJ, Carter, KJ, Sims, LP, Lafleur, B, Fingleton, B, Matrisian, LM A protective role of mast cells in intestinal tumorigenesis. Carcinogenesis, 29(4), 880-6, 2008.
- Martin, MD, Carter, KJ, Jean-Philippe, SR, Chang, M, Mobashery, S, Thiolloy, S, Lynch, CC, Matrisian, LM, Fingleton, B Effect of ablation or inhibition of stromal matrix metalloproteinase-9 on lung metastasis in a breast cancer model is dependent on genetic background. Cancer Res, 68(15), 6251-9, 2008.
- Martin, MD, Fingleton, B, Lynch, CC, Wells, S, McIntyre, JO, Piston, DW, Matrisian, LM Establishment and quantitative imaging of a 3D lung organotypic model of mammary tumor outgrowth. Clin Exp Metastasis, 25(8), 877-85, 2008.
- Quarles, CC, Lepage, M, Gorden, DL, Fingleton, B, Yankeelov, TE, Price, RR, Matrisian, LM, Gore, JC, McIntyre, JO Functional colonography of Min mice using dark lumen dynamic contrast-enhanced MRI. Magn Reson Med, 60(3), 718-26, 2008.
- Stathopoulos, GT, Sherrill, TP, Han, W, Sadikot, RT, Yull, FE, Blackwell, TS, Fingleton, B Host nuclear factor-kappaB activation potentiates lung cancer metastasis. Mol Cancer Res, 6(3), 364-71, 2008.
- Sinnamon, MJ, Carter, KJ, Fingleton, B, Matrisian, LM Matrix metalloproteinase-9 contributes to intestinal tumourigenesis in the adenomatous polyposis coli multiple intestinal neoplasia mouse. Int J Exp Pathol, 89(6), 466-75, 2008.
- Stathopoulos, GT, Sherrill, TP, Han, W, Sadikot, RT, Polosukhin, VV, Fingleton, B, Yull, FE, Blackwell, TS Use of bioluminescent imaging to investigate the role of nuclear factor-kappaBeta in experimental non-small cell lung cancer metastasis. Clin Exp Metastasis, 25(1), 43-51, 2008.
- Ogden, SR, Wroblewski, LE, Weydig, C, Romero-Gallo, J, O''Brien, DP, Israel, DA, Krishna, US, Fingleton, B, Reynolds, AB, Wessler, S, Peek, RM p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7. Mol Biol Cell, 19(10), 4110-21, 2008.
- Fingleton, B, Powell, WC, Crawford, HC, Couchman, JR, Matrisian, LM A Rat Monoclonal Antibody That Recognizes Pro- And Active MMP-7 Indicates Polarized Expression In Vivo. Hybridoma (Larchmt), 26(1), 22-7, 2007.
- Stathopoulos, GT, Sherrill, TP, Cheng, DS, Scoggins, RM, Han, W, Polosukhin, VV, Connelly, L, Yull, FE, Fingleton, B, Blackwell, TS Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Proc Natl Acad Sci U S A, 104(47), 18514-9, 2007.
- 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 Hu/Mu ProtIn oligonucleotide microarray: dual-species array for profiling protease and protease inhibitor gene expression in tumors and their microenvironment. Mol Cancer Res, 5(5), 443-54, 2007.
- Fingleton, B, Carter, KJ, Matrisian, LM Loss of functional Fas ligand enhances intestinal tumorigenesis in the Min mouse model. Cancer Res, 67(10), 4800-6, 2007.
- Fingleton, B MMPs as therapeutic targets-Still a viable option. Semin Cell Dev Biol, 2007.
- Lynch, CC, Vargo-Gogola, T, Martin, MD, Fingleton, B, Crawford, HC, Matrisian, LM Matrix Metalloproteinase 7 Mediates Mammary Epithelial Cell Tumorigenesis through the ErbB4 Receptor. Cancer Res, 67(14), 6760-7, 2007.
- Fingleton, B Matrix metalloproteinases as valid clinical targets. Curr Pharm Des, 13(3), 333-46, 2007.
- Fingleton, B Molecular targets in metastasis: lessons from genomic approaches. Cancer Genomics Proteomics, 4(3), 211-21, 2007.
- Lepage, M, Dow, WC, Melchior, M, You, Y, Fingleton, B, Quarles, CC, PÃ©pin, C, Gore, JC, Matrisian, LM, McIntyre, JO Noninvasive detection of matrix metalloproteinase activity in vivo using a novel magnetic resonance imaging contrast agent with a solubility switch. Mol Imaging, 6(6), 393-403, 2007.
- Gorden, DL, Fingleton, B, Crawford, HC, Jansen, DE, Lepage, M, Matrisian, LM Resident stromal cell-derived MMP-9 promotes the growth of colorectal metastases in the liver microenvironment. Int J Cancer, 2007.
- Acuff, HB, Sinnamon, M, Fingleton, B, Boone, B, Levy, SE, Chen, X, Pozzi, A, Carbone, DP, Schwartz, DR, Moin, K, Sloane, BF, Matrisian, LM 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. Cancer Res, 66(16), 7968-75, 2006.
- Acuff, HB, Carter, KJ, Fingleton, B, Gorden, DL, Matrisian, LM Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment. Cancer Res, 66(1), 259-66, 2006.
- Fingleton, B Matrix metalloproteinases: roles in cancer and metastasis. Front Biosci, 11479-91, 2006.
- Chen, X, Su, Y, Fingleton, B, Acuff, H, Matrisian, LM, Zent, R, Pozzi, A An orthotopic model of lung cancer to analyze primary and metastatic NSCLC growth in integrin alpha1-null mice. Clin Exp Metastasis, 22(2), 185-93, 2005.
- Chen, X, Su, Y, Fingleton, B, Acuff, H, Matrisian, LM, Zent, R, Pozzi, A Increased plasma MMP9 in integrin alpha1-null mice enhances lung metastasis of colon carcinoma cells. Int J Cancer, 116(1), 52-61, 2005.
- 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 MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell, 7(5), 485-96, 2005.
- Harrell, PC, McCawley, LJ, Fingleton, B, McIntyre, JO, Matrisian, LM Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells. Exp Cell Res, 303(2), 308-20, 2005.
- Mohammed, FF, Smookler, DS, Taylor, SE, Fingleton, B, Kassiri, Z, Sanchez, OH, English, JL, Matrisian, LM, Au, B, Yeh, WC, Khokha, R Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet, 36(9), 969-77, 2004.
- McIntyre, JO, Fingleton, B, Wells, KS, Piston, DW, Lynch, CC, Gautam, S, Matrisian, LM Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. Biochem J, 377(Pt 3), 617-28, 2004.
- Yang, L, DeBusk, LM, Fukuda, K, Fingleton, B, Green-Jarvis, B, Shyr, Y, Matrisian, LM, Carbone, DP, Lin, PC Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell, 6(4), 409-21, 2004.
- Fingleton, B, Menon, R, Carter, KJ, Overstreet, PD, Hachey, DL, Matrisian, LM, McIntyre, JO Proteinase activity in human and murine saliva as a biomarker for proteinase inhibitor efficacy. Clin Cancer Res, 10(23), 7865-74, 2004.
- Gustavson, MD, Crawford, HC, Fingleton, B, Matrisian, LM Tcf binding sequence and position determines beta-catenin and Lef-1 responsiveness of MMP-7 promoters. Mol Carcinog, 41(3), 125-39, 2004.
- Hulboy, DL, Gautam, S, Fingleton, B, Matrisian, LM The influence of matrix metalloproteinase-7 on early mammary tumorigenesis in the multiple intestinal neoplasia mouse. Oncol Rep, 12(1), 13-7, 2004.
- Fingleton, B CMT-3. CollaGenex. Curr Opin Investig Drugs, 4(12), 1460-7, 2003.
- Fingleton, B Matrix metalloproteinase inhibitors for cancer therapy:the current situation and future prospects. Expert Opin Ther Targets, 7(3), 385-97, 2003.
- Vargo-Gogola, T, Crawford, HC, Fingleton, B, Matrisian, LM Identification of novel matrix metalloproteinase-7 (matrilysin) cleavage sites in murine and human Fas ligand. Arch Biochem Biophys, 408(2), 155-61, 2002.
- Vargo-Gogola, T, Fingleton, B, Crawford, HC, Matrisian, LM Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo. Cancer Res, 62(19), 5559-63, 2002.
- Fingleton, B, Vargo-Gogola, T, Crawford, HC, Matrisian, LM Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Neoplasia, 3(6), 459-68, 2002.
- Coussens, LM, Fingleton, B, Matrisian, LM Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science, 295(5564), 2387-92, 2002.
- Fingleton, B, Matrisian, LM Matrix metalloproteinases as targets for therapy in Kaposi sarcoma. Curr Opin Oncol, 13(5), 368-73, 2001.
- NoÃ«, V, Fingleton, B, Jacobs, K, Crawford, HC, Vermeulen, S, Steelant, W, Bruyneel, E, Matrisian, LM, Mareel, M Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci, 114(Pt 1), 111-118, 2001.
- Crawford, HC, Fingleton, B, Gustavson, MD, Kurpios, N, Wagenaar, RA, Hassell, JA, Matrisian, LM The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol Cell Biol, 21(4), 1370-83, 2001.
- Haro, H, Crawford, HC, Fingleton, B, MacDougall, JR, Shinomiya, K, Spengler, DM, Matrisian, LM Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption. J Clin Invest, 105(2), 133-41, 2000.
- Haro, H, Crawford, HC, Fingleton, B, Shinomiya, K, Spengler, DM, Matrisian, LM Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption. J Clin Invest, 105(2), 143-50, 2000.
- Nelson, AR, Fingleton, B, Rothenberg, ML, Matrisian, LM Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol, 18(5), 1135-49, 2000.
- Fingleton, BM, Heppner Goss, KJ, Crawford, HC, Matrisian, LM Matrilysin in early stage intestinal tumorigenesis. APMIS, 107(1), 102-10, 1999.
- Crawford, HC, Fingleton, BM, Rudolph-Owen, LA, Goss, KJ, Rubinfeld, B, Polakis, P, Matrisian, LM The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene, 18(18), 2883-91, 1999.
- Powell, WC, Fingleton, B, Wilson, CL, Boothby, M, Matrisian, LM The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Curr Biol, 9(24), 1441-7, 1999.
- Fingleton, B, McDonnell, S Cytokine regulation of matrilysin gene expression. Biochem Soc Trans, 25(2), 155S, 1997.
- McDonnell, S, Fingleton, B Role of matrix metalloproteinases in invasion and metastasis: biology, diagnosis and inhibitors. Cytotechnology, 12(1-3), 367-84, 1993.