Center for Matrix Biology - Vanderbilt University and Medical Center

Lynn M. Matrisian, Ph.D.
Professor in the Department of Cancer Biology

	Office Address:	23rd and Pierce Avenues
	Mailing Address:	23rd and Pierce Avenues Nashville, TN 37232-6840
	Lab address:	770 Preston Research Building
	Phone:	615-322-0375
		email

Research Summary

We are interested in understanding the molecular mechanism that underlie cancer development, growth, and metastasis. Our approach involves a combination of cell biology, molecular biology, and whole animal techniques.

We have determined that growth factors and cancer-causing oncogenes induce the expression of genes for extracellular matrix-degrading metalloproteinases (MMPs). These enzymes are capable of degrading basement membrane and connective tissue proteins, and have been associated with tumor invasion and metastasis. In addition, these enzymes contribute to many stages of tumor progression, including the growth and development of early stage tumors and angiogenesis. Their substrates are much broader than matrix components alone, and include growth factors and their receptors, chemokines, apoptosis factors, and adhesion molecules. We are using in vitro and in vivo model systems, including genetically altered transgenic or "knock-out" mice, to examine the role of metalloproteinases in specific stages of cancer.

We have been exploring the application of MMP-sensitive protease switch as a component of multifunctional nanoparticles for the detection and treatment of cancer. Near infrared optical "beacons", MRI, and SPECT contrast agents have been attached to peptide sequences that are cleaved by specific MMP family members, resulting in enhanced visualization of tumors based on elevated proteolytic activity. These probes have been attached to dendrimer backbones, resulting in nanostructures that detect proteolytic activity. We are extending these nanoparticles to include toxic drugs that are activated in the presence of tumor proteolytic activity.

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Associated initiative(s):

Tumor Microenvironment

Career opportunities:
None currently available

Selected Publications

» Thiolloy, S, Halpern, J, Holt, GE, Schwartz, HS, Mundy, GR, Matrisian, LM, Lynch, CC Osteoclast-derived matrix metalloproteinase-7, but not matrix metalloproteinase-9, contributes to tumor-induced osteolysis Cancer Res 2009. 69:6747-55

» McIntyre, JO, Matrisian, LM Optical proteolytic beacons for in vivo detection of matrix metalloproteinase activity Methods Mol Biol 2009. 539:155-74

» Scherer, RL, VanSaun, MN, McIntyre, JO, Matrisian, LM Optical imaging of matrix metalloproteinase-7 activity in vivo using a proteolytic nanobeacon Mol Imaging 2009. 7:118-31

» McCawley, LJ, Wright, J, LaFleur, BJ, Crawford, HC, Matrisian, LM Keratinocyte expression of MMP3 enhances differentiation and prevents tumor establishment Am J Pathol 2008. 173:1528-39

» 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 2008. 89:466-75

» Sinnamon, MJ, Carter, KJ, Sims, LP, Lafleur, B, Fingleton, B, Matrisian, LM A protective role of mast cells in intestinal tumorigenesis Carcinogenesis 2008. 29:880-6

» 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 2008. 68:6251-9

» 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 2008. 25:877-85

» L??pez-Ot?-n, C, Matrisian, LM Emerging roles of proteases in tumour suppression Nat Rev Cancer 2007. 7:800-8

» 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 2007. 6:393-403

» 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 2007. 67:6760-7

» Fingleton, B, Carter, KJ, Matrisian, LM Loss of functional fas ligand enhances intestinal tumorigenesis in the min mouse model Cancer Res 2007. 67:4800-6

» 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 2006. 66:259-66

» 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 2006. 66:7968-75

» 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 2005. 7:485-96

» Coussens, L.M., Fingleton, B., and Matrisian, L.M Matrix Metalloproteinase Inhibitors and Cancer: Trials and Tribulations Science 2002. 295:2387-2392

» Brinckerhoff, C.E., and Matrisian, L.M Matrix Metalloproteinases: a tail of a frog that became a prince Nature Reviews: Molecular Cell Biology 2002. 3:207-214