Vanderbilt University School of
715CA PRB [office]/ 734 PRB [lab]
771 PRB 37232-6840
Inflammation, Proteolysis, colitis, IL4, IL13, MMP10, colon cancer,Cancer,Enzyme action,Knockout,Malignancy,Mouse
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. Inflammatory proteinase slips into tumor cells. Nat Med, 16(2), 161-3, 2010. PMCID:2902104
Fingleton, B, Lynch, CC. A new dress code for MMPs: cleavage optional. Dev Cell, 18(1), 3-4, 2010.
Koller, FL, Hwang, DG, Dozier, EA, Fingleton, B. Epithelial interleukin-4 receptor expression promotes colon tumor growth. Carcinogenesis, 31(6), 1010-7, 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, 2010, 530745, 2010. PMCID:2902104
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.
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. PMCID:2902104
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. PMCID:2588650
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. PMCID:2555941
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. PMCID:2646120
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.
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.
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.
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.
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.
Fingleton, B. MMPs as therapeutic targets-Still a viable option. Semin Cell Dev Biol, , , 2007. PMCID:2677300
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, 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.
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.
Lepage, M, Dow, WC, Melchior, M, You, Y, Fingleton, B, Quarles, CC, P??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.
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.
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.
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. PMCID:2141808
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. PMCID:1360653
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.
Fingleton, B. Matrix metalloproteinases: roles in cancer and metastasis. Front Biosci, 11, 479-91, 2006.
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.
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.
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.
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.
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.
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. PMCID:1223892
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.
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. Matrix metalloproteinase inhibitors for cancer therapy:the current situation
and future prospects. Expert Opin Ther Targets, 7(3), 385-97, 2003.
Fingleton, B. CMT-3. CollaGenex. Curr Opin Investig Drugs, 4(12), 1460-7, 2003.
Coussens, LM, Fingleton, B, Matrisian, LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science, 295(5564), 2387-92, 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. PMCID:1506562
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.
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. PMCID:99589
Fingleton, B, Matrisian, LM. Matrix metalloproteinases as targets for therapy in Kaposi sarcoma. Curr Opin Oncol, 13(5), 368-73, 2001.
No?<, 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.
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. PMCID:377425
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. PMCID:377426
Nelson, AR, Fingleton, B, Rothenberg, ML, Matrisian, LM. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol, 18(5), 1135-49, 2000.
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.
Fingleton, BM, Heppner Goss, KJ, Crawford, HC, Matrisian, LM. Matrilysin in early stage intestinal tumorigenesis. APMIS, 107(1), 102-10, 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.
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