Abstract
Proteolysis has been cited as an important contributor to cancer initiation and progression. One can take advantage of tumor-associated proteases to selectively deliver imaging agents. Protease-activated imaging systems have been developed using substrates designed for hydrolysis by members of the matrix metalloproteinase (MMP) family. We presently describe approaches by which one can optically image matrix metalloproteinase activity implicated in breast cancer progression, with consideration of selective versus broad protease probes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67
Deryugina EI, Quigley JP (2010) Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: contrasting, overlapping and compensatory functions. Biochim Biophys Acta 1803:103–120
Gialeli C, Theocharis AD, Karamanos NK (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 278:16–27
Rha SY, Kim JH, Roh JK, Lee KS, Min JS, Kim BS, Chung HC (1997) Sequential production and activation of matrix metalloproteinase-9 (MMP-9) with breast cancer progression. Breast Cancer Res Treat 43:175–181
Vihinen P, Ala-aho R, Kahari V-M (2005) Matrix metalloproteinases as therapeutic targets in cancer. Curr Cancer Drug Targets 5:203–220
Somiari SB, Somiari RI, Heckman CM, Olsen CH, Jordan RM, Russell SJ, Shriver CD (2006) Circulating MMP2 and MMP9 in breast cancer - potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer 119:1403–1411
McGowan PM, Duffy MJ (2008) Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database. Ann Oncol 19:1566–1572
Köhrmann A, Kammerer U, Kapp M, Dietl J, Anacker J (2009) Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: new findings and review of the literature. BMC Cancer 9:188
Figueira RCS, Gomes LR, Neto JS, Silva FC, Silva IDCG, Sodayar MC (2009) Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer 9:20
Eck SM, Hoopes PJ, Petrella BL, Coon CI, Brinckerhoff CE (2009) Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model. Breast Cancer Res Treat 116:79
Wyatt CA, Geoghegan JC, Brinckerhoff CE (2005) Short hairpin RNA-mediated inhibition of matrix metalloproteinase-1 in MDA-231 cells: effects on matrix destruction and tumor growth. Cancer Res 65:11101–11108
Liu H, Kato Y, Erzinger SA, Kiriakova GM, Qian Y, Palmieri D, Steeg PS, Price JE (2012) The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model. BMC Cancer 12:583
Ohshiba T, Miyaura C, Inada M, Ito A (2003) Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis. Br J Cancer 88:1318–1326
Decock J, Thirkettle S, Wagstaff L, Edwards DR (2011) Matrix metalloproteinases: protective roles in cancer. J Cell Mol Med 15:1254–1265
Martin MD, Matrisian LM (2007) The other side of MMPs: protective roles in tumor progression. Cancer Metastasis Rev 26:717–724
Dufour A, Overall CM (2013) Missing the target: matrix metalloproteinase antitargets in inflammation and cancer. Trends Pharm Sci 34:233–242
Morrison C, Mancini S, Cipollone J, Kappelhoff R, Roskelley C, Overall C (2011) Microarray and proteomic analysis of breast cancer cell and osteoblast co-cultures: role of osteoblast matrix metalloproteinase (MMP)-13 in bone metastasis. J Biol Chem 286:34271–34285
Zarrabi K, Dufour A, Li J, Kuscu C, Pulkoski-Gross A, Zhi J, Hu Y, Sampson NS, Zucker S, Cao J (2011) Inhibition of matrix metalloproteinase-14 (MMP-14)-mediated cancer cell migration. J Biol Chem 286:33167–33177
Fields GB (2008) Protease-activated delivery and imaging systems. In: Edwards D, Hoyer-Hansen G, Blasi F, Sloane B (eds) The cancer degradome – proteases in cancer biology. Springer, New York, NY, pp 827–851
Knapinska A, Fields GB (2012) Chemical biology for understanding matrix metalloproteinase function. ChemBioChem 13:2002–2020
Li C, Wang W, Wu Q, Ke S, Houston J, Sevick-Muraca E, Dong L, Chow D, Charnsangavej C, Gelovani JG (2006) Dual optical and nuclear imaging in human melanoma xenografts using a single targeted imaging probe. Nucl Med Biol 33:349–358
Piao D, Xie H, Zhang W, Krasinski JS, Zhang G, Dehghani H, Pogue BW (2006) Endoscopic, rapid near-infrared optical tomography. Opt Lett 31:2876–2878
Rudin M, Weissleder R (2003) Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2:123–131
Weissleder R (2002) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2:11–18
Tung C-H (2004) Fluorescent peptide probes for in vivo diagnostic imaging. Biopolymers 76:391–403
Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333
Bremer C, Ntzachristos V, Weisslender R (2003) Optical-based molecular imaging: contrast agents and potential medical applications. Eur Radiol 13:231–243
Bremer C, Bredow S, Mahmood U, Weissleder R, Tung CH (2001) Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model. Radiology 221:523–529
Bremer C, Tung C-H, Weissleder R (2001) In vivo molecular target assessment of matrix metalloproteinase activity. Nat Med 7:743–748
Clapper ML, Hensley HH, Chang WC, Devarajan K, Nguyen MT, Cooper HS (2011) Detection of colorectal adenomas using a bioactivatable probe specific for matrix metalloproteinase activity. Neoplasia 13:685–691
Xie BW, Mol IM, Keereweer S, van Beek ER, Que I, Snoeks TJ, Chan A, Kaijzel EL, Löwik CW (2012) Dual-wavelength imaging of tumor progression by activatable and targeting near-infrared fluorescent probes in a bioluminescent breast cancer model. PLoS One 7:e31875
Barber PA, Rushforth D, Agrawal S, Tuor UI (2012) Infrared optical imaging of matrix metalloproteinases (MMPs) up regulation following ischemia reperfusion is ameliorated by hypothermia. BMC Neurosci 13:76
Lee S, Park K, Lee S-Y, Ryu JH, Park JW, Ahn HJ, Kwon IC, Youn I-C, Kim K, Choi K (2008) Dark quenched matrix metalloproteinase fluorogenic probe for imaging osteoarthritis development in vivo. Bioconjug Chem 19:1743–1747
Ryu JH, Lee A, Na JH, Lee S, Ahn HJ, Park JW, Ahn CH, Kim BS, Kwon IC, Choi K, Youn I, Kim K (2011) Optimization of matrix metalloproteinase fluorogenic probes for osteoarthritis imaging. Amino Acids 41:1113–1122
Lim NH, Meinjohanns E, Meldal M, Bou-Gharios G, Nagase H (2014) In vivo imaging of MMP-13 activity in the murine destabilised medial meniscus surgical model of osteoarthritis. Osteoarthritis Cartilage 22:862–868
Lim NH, Meinjohanns E, Bou-Gharios G, Gompels LL, Nuti E, Rossello A, Devel L, Dive V, Meldal M, Nagase H (2014) In vivo imaging of matrix metalloproteinase 12 and matrix metalloproteinase 13 activities in the mouse model of collagen-induced arthritis. Arthritis Rheum 66:589–598
Woodhead-Galloway J (1980) Collagen: the anatomy of a protein. Edward Arnold Limited, London, pp 10–19
Shoulders MD, Raines RT (2009) Collagen structure and stability. Annu Rev Biochem 78:929–958
Fields GB, Prockop DJ (1996) Perspectives on the synthesis and application of triple-helical, collagen-model peptides. Biopolymers 40:345–357
Fields GB (2010) Synthesis and biological applications of collagen-model triple-helical peptides. Org Biomol Chem 8:1237–1258
Jenkins CL, Raines RT (2002) Insights on the conformational stability of collagen. Nat Prod Rep 19:49–59
Brodsky B, Shah NK (1995) The triple-helix motif in proteins. FASEB J 9:1537–1546
Koide T (2005) Triple helical collagen-like peptides: engineering and applications in matrix biology. Connect Tissue Res 46:131–141
Koide T (2007) Designed triple-helical peptides as tools for collagen biochemistry and matrix engineering. Phil Trans R Soc B 362:1281–1291
Brodsky B, Thiagarajan G, Madhan B, Kar K (2008) Triple-helical peptides: an approach to collagen conformation, stability, and self-association. Biopolymers 89:345–353
Lauer-Fields JL, Broder T, Sritharan T, Nagase H, Fields GB (2001) Kinetic analysis of matrix metalloproteinase triple-helicase activity using fluorogenic substrates. Biochemistry 40:5795–5803
Lauer-Fields JL, Kele P, Sui G, Nagase H, Leblanc RM, Fields GB (2003) Analysis of matrix metalloproteinase activity using triple-helical substrates incorporating fluorogenic L- or D-amino acids. Anal Biochem 321:105–115
Lauer-Fields JL, Sritharan T, Stack MS, Nagase H, Fields GB (2003) Selective hydrolysis of triple-helical substrates by matrix metalloproteinase-2 and -9. J Biol Chem 278:18140–18145
Minond D, Lauer-Fields JL, Nagase H, Fields GB (2004) Matrix metalloproteinase triple-helical peptidase activities are differentially regulated by substrate stability. Biochemistry 43:11474–11481
Minond D, Lauer-Fields JL, Cudic M, Overall CM, Pei D, Brew K, Visse R, Nagase H, Fields GB (2006) The roles of substrate thermal stability and P2 and P1′ subsite identity on matrix metalloproteinase triple-helical peptidase activity and collagen specificity. J Biol Chem 281:38302–38313
Minond D, Lauer-Fields JL, Cudic M, Overall CM, Pei D, Brew K, Moss ML, Fields GB (2007) Differentiation of secreted and membrane-type matrix metalloproteinase activities based on substitutions and interruptions of triple-helical sequences. Biochemistry 46:3724–3733
Lauer-Fields JL, Chalmers MJ, Busby SA, Minond D, Griffin PR, Fields GB (2009) Identification of specific hemopexin-like domain residues that facilitate matrix metalloproteinase collagenolytic activity. J Biol Chem 284:24017–24024
Bhaskaran R, Palmier MO, Lauer-Fields JL, Fields GB, Van Doren SR (2008) MMP-12 catalytic domain recognizes triple-helical peptide models of collagen V with exosites and high activity. J Biol Chem 283:21779–21788
Lee H, Mason JC, Achilefu S (2006) Heptamethine cyanine dyes with a robust C-C bond at the central position of the chromophore. J Org Chem 71:7862–7865
Akers WJ, Xu B, Lee H, Sudlow GP, Fields GB, Achilefu S, Edwards WB (2012) Detection of MMP-2 and MMP-9 activity in vivo with a triple-helical peptide optical probe. Bioconjug Chem 23:656–663
Zhang X, Bresee J, Fields GB, Edwards WB (2014) Near-infrared triple-helical peptide with quenched fluorophores for optical imaging of MMP-2 and MMP-9 proteolytic activity in vivo. Bioorg Med Chem Lett 24:3786–3790
Achilefu S, Jimenez HN, Dorshow RB, Bugaj JE, Webb EG, Wilhelm RR, Rajagopalan R, Johler J, Erion JL (2002) Synthesis, in vitro receptor binding, and in vivo evaluation of fluorescein and carbocyanine peptide-based optical contrast agents. J Med Chem 45:2003–2015
Berezin MY, Guo K, Akers W, Livingston J, Solomon M, Lee H, Liang K, Agee A, Achilefu S (2011) Rational approach to select small peptide molecular probes labeled with fluorescent cyanine dyes for in vivo optical imaging. Biochemistry 50:2691–2700
Zhang Z, Fan J, Cheney PP, Berezin MY, Edwards WB, Akers WJ, Shen D, Liang K, Culver JP, Achilefu S (2009) Activatable molecular systems using homologous near-infrared fluorescent probes for monitoring enzyme activities in vitro, in cellulo, and in vivo. Mol Pharm 6:416–427
Gonzalez LO, Pidal I, Junquera S, Corte MD, Vazquez J, Rodriguez JC, Lamelas ML, Merino AM, Garcia-Muniz JL, Vizoso FJ (2007) Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse. Br J Cancer 97:957–963
Zhang X, Bresee J, Cheney PP, Xu B, Bhowmick M, Cudic M, Fields GB, Edwards WB (2014) Evaluation of a triple-helical peptide with quenched fluorophores for optical imaging of MMP-2 and MMP-9 proteolytic activity. Molecules 19:8571–8588
Fischer R, Mader O, Jung G, Brock R (2003) Extending the applicability of carboxyfluorescein in solid-phase synthesis. Bioconjug Chem 14:653–660
Höfle G, Steglich W, Vorbrüggen H (1978) 4-Dialkylaminopyridines as highly active acylation catalysts. Angew Chem Int Ed Engl 17:569–583
Xu S, Held I, Kempf B, Mayr H, Steglich W, Zipse H (2005) The DMAP-catalyzed acetylation of alcohols—a mechanistic study. Chemistry 11:4751–4757
Yang J, Zhang Z, Lin J, Lu J, Liu BF, Zeng S, Luo Q (2007) Detection of MMP activity in living cells by a genetically encoded surface-displayed FRET sensor. Biochim Biophys Acta 1773:400–407
Zhang Z, Yang J, Lu J, Lin J, Zeng S, Luo Q (2008) Fluorescence imaging to assess the matrix metalloproteinase activity and its inhibitor in vivo. J Biomed Opt 13:011006
Zhu L, Wang H, Wang L, Wang Y, Jiang K, Li C, Ma Q, Gao S, Wang L, Li W, Cai M, Wang H, Niu G, Lee S, Yang W, Fang X, Chen X (2011) High-affinity peptide against MT1-MMP for in vivo tumor imaging. J Control Release 150:248–255
Zhu L, Zhang F, Ma Y, Liu G, Kim K, Fang X, Lee S, Chen X (2011) In vivo optical imaging of membrane-type matrix metalloproteinase (MT-MMP) activity. Mol Pharmaceut 8:2331–2338
Hanaoka H, Mukai T, Habashita S, Asano D, Ogawa K, Kuroda Y, Akizawa H, Iida Y, Endo K, Saga T, Saji H (2007) Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors. Nucl Med Biol 34:503–510
Sprague JE, Li WP, Liang K, Achilefu S, Anderson CJ (2006) In vitro and in vivo investigation of matrix metalloproteinase expression in metastatic tumor models. Nucl Med Biol 33:227–237
Watkins GA, Jones EF, Shell MS, VanBrocklin HF, Pan M-H, Hanrahan SM, Feng JJ, He J, Sounni NE, Dill KA, Contag CH, Coussens LM, Franc BL (2009) Development of an optimized activatable MMP-14 targeted SPECT imaging probe. Bioorg Med Chem 17:653–659
Temma T, Sano K, Kuge Y, Kamihashi J, Takai N, Ogawa Y, Saji H (2009) Development of a radiolabeled probe for detecting membrane type-1 matrix metalloproteinase on malignant tumors. Biol Pharm Bull 32:1272–1277
Ye Y, Bloch S, Achilefu S (2004) Polyvalent carbocyanine molecular beacons for molecular recognitions. J Am Chem Soc 126:7740–7741
Fields CG, Lovdahl CM, Miles AJ, Matthias-Hagen VL, Fields GB (1993) Solid-phase synthesis and stability of triple-helical peptides incorporating native collagen sequences. Biopolymers 33:1695–1707
Fields CG, Mickelson DJ, Drake SL, McCarthy JB, Fields GB (1993) Melanoma cell adhesion and spreading activities of a synthetic 124-residue triple-helical “mini-collagen”. J Biol Chem 268:14153–14160
Grab B, Miles AJ, Furcht LT, Fields GB (1996) Promotion of fibroblast adhesion by triple-helical peptide models of type I collagen-derived sequences. J Biol Chem 271:12234–12240
Lauer-Fields JL, Tuzinski KA, Shimokawa K, Nagase H, Fields GB (2000) Hydrolysis of triple-helical collagen peptide models by matrix metalloproteinases. J Biol Chem 275:13282–13290
Lauer-Fields JL, Nagase H, Fields GB (2000) Use of Edman degradation sequence analysis and matrix-assisted laser desorption/ionization mass spectrometry in designing substrates for matrix metalloproteinases. J Chromatogr A 890:117–125
Malkar NB, Lauer-Fields JL, Borgia JA, Fields GB (2002) Modulation of triple-helical stability and subsequent melanoma cellular responses by single-site substitution of fluoroproline derivatives. Biochemistry 41:6054–6064
Yu Y-C, Tirrell M, Fields GB (1998) Minimal lipidation stabilizes protein-like molecular architecture. J Am Chem Soc 120:9979–9987
Yu Y-C, Berndt P, Tirrell M, Fields GB (1996) Self-assembling amphiphiles for construction of protein molecular architecture. J Am Chem Soc 118:12515–12520
Schneider CA, Rasband WS, Eliceiri KW (2012) NIH image to ImageJ: 25 years of image analysis. Nat Methods 9(7):671–675
Guy CA, Fields GB (1997) Trifluoroacetic acid cleavage and deprotection of resin-bound peptides following synthesis by Fmoc chemistry. Methods Enzymol 289:67–83
Acknowledgments
The methods described in this chapter reflect the pioneering work of the laboratories of Drs. Ralph Weissleder and W. Barry Edwards. We gratefully acknowledge the National Institutes of Health (EB000289 and CA098799) and the Texas Higher Education STAR Award Program for support of our laboratory’s research on matrix metalloproteinases.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Fields, G.B., Stawikowski, M.J. (2016). Imaging Matrix Metalloproteinase Activity Implicated in Breast Cancer Progression. In: Cao, J. (eds) Breast Cancer. Methods in Molecular Biology, vol 1406. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3444-7_25
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3444-7_25
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3442-3
Online ISBN: 978-1-4939-3444-7
eBook Packages: Springer Protocols