Abstract
Perfusion is seriously hampered in solid tumors that overexpress extracellular matrix components like hyaluronic acid, collagen and chondroitin sulfate. Tumor penetration of circulating material is most affected for nanocarriers because of their size and lower diffusion. Due to this, the aid of enzymes that degrade the matrix becomes essential when applying nanocarrier based anticancer therapies like oncolytic viruses or nano-formulated drugs like Abraxane or Doxil.
In the case of hyaluronic acid and chondroitin sulfate, these biomacromolecules bind water very tightly and as a consequence of this, tumors that abound in them have an elevated resistance to a contacting fluid. In the case of collagen, the dense molecular network represents a physical barrier for any nanocarrier and also compresses the tumor vessels obstructing perfusion. Drug penetration and therapeutic index increase when anticancer therapies are combined with enzymes that specifically degrade the over-expressed matrix component.
This chapter will cover the use of matrix degrading enzymes for enhancing the delivery of nanocarriers, including oncolytic viruses and synthetic nanoparticles. Ongoing clinical trials will be discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- HA:
-
hyaluronic acid
- Hyal:
-
hyaluronidase
- IFP:
-
interstitial fluid pressure
- GFP:
-
green fluorescent protein
- ECM:
-
extracellular matrix
- b-HABP:
-
biotynilated hyaluronic acid binding protein
- CSPG:
-
chondroitin sulfate proteoglycan
- PDA, PDAC:
-
Pancreatic ductal adenocarcinoma
- FDA:
-
Food and drug administration
- OV:
-
Oncolytic virus
- Chase:
-
Chondroitinase
References
Alkrad JA, Mrestani Y, Stroehl D et al (2003) Characterization of enzymatically digested hyaluronic acid using NMR, Raman, IR, and UV-vis spectroscopies. J Pharm Biomed Anal 31:545–550. doi:10.1016/S0731-7085(02)00682-9
Armstrong T, Packham G, Murphy LB et al (2004) Type I collagen promotes the malignant phenotype of pancreatic ductal adenocarcinoma. Clin Cancer Res 10:7427–7437. doi:10.1158/1078-0432.CCR-03-0825
Asimakopoulou AP, Theocharis AD, Tzanakakis GN, Karamanos NK (2008) The biological role of chondroitin sulfate in cancer and chondroitin-based anticancer agents. In Vivo (Brooklyn) 22:385–390
Bauer S, Arpa-Sancet MP, Finlay JA et al (2013) Adhesion of marine fouling organisms on hydrophilic and amphiphilic polysaccharides. Langmuir 29:4039–4047. doi:10.1021/la3038022
Baumgartner G, Gomar-Höss C, Sakr L et al (1998) The impact of extracellular matrix on the chemoresistance of solid tumors – experimental and clinical results of hyaluronidase as additive to cytostatic chemotherapy. Cancer Lett 131:85–99. doi:10.1016/S0304-3835(98)00204-3
Beckenlehner K, Bannke S, Spruss T et al (1992) Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo. J Cancer Res Clin Oncol 118:591–596. doi:10.1007/BF01211802
Berchtold S, Grünwald B, Krüger A et al (2015) Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma. Cancer Lett 356:721–732. doi:10.1016/j.canlet.2014.10.020
Bisno AL, Brito MO, Collins CM (2003) Molecular basis of group A streptococcal virulence. Lancet Infect Dis 3:191–200. doi:10.1016/S1473-3099(03)00576-0
Blache CA, Manuel ER, Kaltcheva TI et al (2012) Systemic delivery of Salmonella typhimurium transformed with IDO shRNA enhances intratumoral vector colonization and suppresses tumor growth. Cancer Res 72:6447–6456. doi:10.1158/0008-5472.CAN-12-0193
Botella P, Abasolo I, Fernández Y et al (2011) Surface-modified silica nanoparticles for tumor-targeted delivery of camptothecin and its biological evaluation. J Control Release 156:246–257. doi:10.1016/j.jconrel.2011.06.039
Brekken C, de Lange DC (1998) Hyaluronidase reduces the interstitial fluid pressure in solid tumours in a non-linear concentration-dependent manner. Cancer Lett 131:65–70
Brekken C, Hjelstuen MH, Bruland ØS, de Lange DC (2000) Hyaluronidase-induced periodic modulation of the interstitial fluid pressure increases selective antibody uptake in human osteosarcoma xenografts. Anticancer Res 20:3513–3519
Caruso F, Lichtenfeld H, Donath E, Möhwald H (1999) Investigation of electrostatic interactions in polyelectrolyte multilayer films: binding of anionic fluorescent probes to layers assembled onto colloids. Macromolecules 32:2317–2328. doi:10.1021/ma980674i
Chauhan VP, Martin JD, Liu H et al (2013) Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat Commun 4:2516. doi:10.1038/ncomms3516
Choi J (2006) Intraperitoneal immunotherapy for metastatic ovarian carcinoma: resistance of intratumoral collagen to antibody penetration. Clin Cancer Res 12:1906–1912. doi:10.1158/1078-0432.CCR-05-2141
Cun X, Ruan S, Chen J et al (2015) Acta Biomaterialia A dual strategy to improve the penetration and treatment of breast cancer by combining shrinking nanoparticles with collagen depletion by losartan. ACTA Biomater 31:186. doi:10.1016/j.actbio.2015.12.002
Curnis F, Sacchi A, Borgna L et al (2000) Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol 18:1185–1190. doi:10.1038/81183
Decher G (1997) Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 277:1232–1237. doi:10.1126/science.277.5330.1232
Diop-Frimpong B, Chauhan VP, Krane S et al (2011) Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. Proc Natl Acad Sci U S A 108:2909–2914. doi:10.1073/pnas.1018892108
Dmitrieva N, Yu L, Viapiano M et al (2011) Chondroitinase ABC I-mediated enhancement of oncolytic virus spread and antitumor efficacy. Clin Cancer Res 17:1362–1372. doi:10.1158/1078-0432.CCR-10-2213
Dunn AL, Heavner JE, Racz G, Day M (2010) Hyaluronidase: a review of approved formulations, indications and off-label use in chronic pain management. Expert Opin Biol Ther 10:127–131. doi:10.1517/14712590903490382
Dychter SS, Harrigan R, Bahn JD et al (2014) Tolerability and pharmacokinetic properties of ondansetron administered subcutaneously with recombinant human hyaluronidase in minipigs and healthy volunteers. Clin Ther 36:211–224. doi:10.1016/j.clinthera.2013.12.013
Eikenes L, Tari M, Tufto I et al (2005) Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx) in human osteosarcoma xenografts. Br J Cancer 93:81–88. doi:10.1038/sj.bjc.6602626
Fadnes HO, Reed RK, Aukland K (1977) Interstitial fluid pressure in rats measured with a modified wick technique. Microvasc Res 14:27–36. doi:10.1016/0026-2862(77)90138-8
Fraser JR, Laurent TC (1989) Turnover and metabolism of hyaluronan. Ciba Found Symp 143:41–49, 281–285
Ganesh S, Gonzalez-Edick M, Gibbons D et al (2008) Intratumoral coadministration of hyaluronidase enzyme and oncolytic adenoviruses enhances virus potency in metastatic tumor models. Clin Cancer Res 14:3933–3941. doi:10.1158/1078-0432.CCR-07-4732
Goodman TT, Olive PL, Pun SH (2007) Increased nanoparticle penetration in collagenase-treated multicellular spheroids. Int J Nanomedicine 2:265–274
Grzesiak JJ, Bouvet M (2006) The alpha2beta1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines. Br J Cancer 94:1311–1319. doi:10.1038/sj.bjc.6603088
Guedan S, Rojas JJ, Gros A et al (2010) Hyaluronidase expression by an oncolytic adenovirus enhances its intratumoral spread and suppresses tumor growth. Mol Ther 18:1275–1283. doi:10.1038/mt.2010.79
Heldin C-H, Rubin K, Pietras K, Östman A (2004) High interstitial fluid pressure — an obstacle in cancer therapy. Nat Rev Cancer 4:806–813. doi:10.1038/nrc1456
Huang Z, Zhao C, Chen Y et al (2014) Recombinant human hyaluronidase PH20 does Not stimulate an acute inflammatory response and inhibits lipopolysaccharide-induced neutrophil recruitment in the air pouch model of inflammation. J Immunol 192:5285–5295. doi:10.4049/jimmunol.1303060
Ioachim E, Charchanti A, Briasoulis E et al (2002) Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression. Eur J Cancer 38:2362–2370. doi:10.1016/S0959-8049(02)00210-1
Jacobetz MA, Chan DS, Neesse A et al (2013) Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 62:112–120. doi:10.1136/gutjnl-2012-302529
Järvinen TAH (2012) Design of target-seeking antifibrotic compounds. Methods Enzymol 509:243–261. doi:10.1016/B978-0-12-391858-1.00013-7
Järvinen TAH, Ruoslahti E (2010) Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice. Proc Natl Acad Sci U S A 107:21671–21676. doi:10.1073/pnas.1016233107
Joo J, Liu X, Kotamraju VR et al (2015) Gated luminescence imaging of silicon nanoparticles. ACS Nano 9:6233–6241. doi:10.1021/acsnano.5b01594
Kimata K, Honma Y, Okayama M et al (1983) Increased synthesis of hyaluronic acid by mouse mammary carcinoma cell variants with high metastatic potential. Cancer Res 43:1347–1354
Kuhn SJ, Finch SK, Hallahan DE, Giorgio TD (2006) Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix. Nano Lett 6:306–312. doi:10.1021/nl052241g
Kultti A, Zhao C, Singha NC et al (2014) Accumulation of extracellular hyaluronan by hyaluronan synthase 3 promotes tumor growth and modulates the pancreatic cancer microenvironment. BioMed Res Int 2014:817613. doi:10.1155/2014/817613
Kuriyama N, Kuriyama H, Julin CM et al (2001) Protease pretreatment increases the efficacy of adenovirus-mediated gene therapy for the treatment of an experimental glioblastoma model advances in brief protease pretreatment increases the efficacy of adenovirus-mediated gene therapy for the treatment o. 1805–1809.
Laborda E, Puig-Saus C, Rodriguez-García A et al (2014) A pRb-responsive, RGD-modified, and hyaluronidase-armed canine oncolytic adenovirus for application in veterinary oncology. Mol Ther 22:986–998. doi:10.1038/mt.2014.7
Laurent UB, Dahl LB, Reed RK (1991) Catabolism of hyaluronan in rabbit skin takes place locally, in lymph nodes and liver. Exp Physiol 76:695–703
Li M-W, Yudin AI, Robertson KR et al (2002) Importance of glycosylation and disulfide bonds in hyaluronidase activity of macaque sperm surface PH-20. J Androl 23:211–219
Lipponen P, Aaltomaa S, Tammi R et al (2001) High stromal hyaluronan level is associated with poor differentiation and metastasis in prostate cancer. Eur J Cancer 37:849–856
Liu D, Pearlman E, Diaconu E et al (1996) Expression of hyaluronidase by tumor cells induces angiogenesis in vivo. Proc Natl Acad Sci U S A 93:7832–7837. doi:10.1073/pnas.93.15.7832
Manuel ER, Chen J, D’Apuzzo M et al (2015) Salmonella-based therapy targeting indoleamine 2,3-Dioxygenase coupled with enzymatic depletion of tumor hyaluronan induces complete regression of aggressive pancreatic tumors. Cancer Immunol Res 3:1096–1107. doi:10.1158/2326-6066.CIR-14-0214
Martínez-Vélez N, Xipell E, Vera B, Acanda de la Rocha A, Zalacain M, Marrodan L, Gonzalez-Huarriz M, Toledo G, Cascallo M, Alemany R, Patiño A, Alonso AM (2016) The oncolytic adenovirus VCN-01 as therapeutic approach against pediatric osteosarcoma. Clin Cancer Res 22(9):2217–2225. doi:10.1158/1078-0432.CCR-15-1899.
McKee TD (2006) Degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic herpes simplex virus vector. Cancer Res 66:2509–2513. doi:10.1158/0008-5472.CAN-05-2242
Mok W, Boucher Y, Jain RK (2007) Matrix metalloproteinases-1 and −8 improve the distribution and efficacy of an oncolytic virus. Cancer Res 67:10664–10668. doi:10.1158/0008-5472.CAN-07-3107
Muckenschnabel I, Bernhardt G, Spruss T, Buschauer A (1996) Hyaluronidase pretreatment produces selective melphalan enrichment in malignant melanoma implanted in nude mice. Cancer Chemother Pharmacol 38:88–94
Nelson DL, Cox MM (2008) Lehninger principles of biochemistry, 5th edn., pp 1–1294
Nugent LJ, Jain RK (1984) Extravascular diffusion in normal and neoplastic tissues. Cancer Res 44:238–244
Pirinen R, Tammi R, Tammi M et al (2001) Prognostic value of hyaluronan expression in non-small-cell lung cancer: increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma. Int J Cancer 95:12–17
Plodinec M, Loparic M, Monnier CA et al (2012) The nanomechanical signature of breast cancer. Nat Nanotechnol 7:757–765. doi:10.1038/nnano.2012.167
Provenzano PP, Cuevas C, Chang AE et al (2012) Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21:418–429
Průšová A, Conte P, Kučerík J, Alonzo G (2010) Dynamics of hyaluronan aqueous solutions as assessed by fast field cycling NMR relaxometry. Anal Bioanal Chem 397:3023–3028. doi:10.1007/s00216-010-3855-9
Ricciardelli C, Brooks JH, Suwiwat S et al (2002) Regulation of stromal versican expression by breast cancer cells and importance to relapse-free survival in patients with node-negative primary breast cancer. Clin Cancer Res 8:1054–1060
Rodriguez-Garcia A, Gimenez-Alejandre M, Rojas JJ et al (2015) Safety and efficacy of VCN-01, an oncolytic adenovirus combining fiber HSG-binding domain replacement with RGD and hyaluronidase expression. Clin Cancer Res 21:1406–1418. doi:10.1158/1078-0432.CCR-14-2213
Rosengren S, Dychter SS, Printz MA et al (2015) Clinical immunogenicity of rHuPH20, a hyaluronidase enabling subcutaneous drug administration. AAPS J 17:1144–1156. doi:10.1208/s12248-015-9782-0
Ruoslahti E (2002) Specialization of tumour vasculature. Nat Rev Cancer 2:83–90. doi:10.1038/nrc724
Sakai S, Hirano K, Toyoda H et al (2007) Matrix assisted laser desorption ionization-time of flight mass spectrometry analysis of hyaluronan oligosaccharides. Anal Chim Acta 593:207–213. doi:10.1016/j.aca.2007.05.005
Scodeller P, Flexer V, Szamocki R et al (2008) Wired-enzyme core-shell Au nanoparticle biosensor. J Am Chem Soc 130:12690–12697. doi:10.1021/ja802318f
Scodeller P, Carballo R, Szamocki R et al (2010) Layer-by-layer self assembled osmium polymer mediated laccase oxygen cathodes for biofuel cells: the role of hydrogen peroxide. J Am Chem Soc 132:11132–11140
Scodeller P, Catalano PN, Salguero N et al (2013) Hyaluronan degrading silica nanoparticles for skin cancer therapy. Nanoscale 5:9690–9698. doi:10.1039/c3nr02787b
Sherman-Baust CA, Weeraratna AT, Rangel LBA et al (2003) Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. Cancer Cell 3:377–386. doi:10.1016/S1535-6108(03)00058-8
Shintani Y, Hollingsworth MA, Wheelock MJ, Johnson KR (2006) Collagen I promotes metastasis in pancreatic cancer by activating c-Jun NH2-terminal kinase 1 and up-regulating N-cadherin expression. Cancer Res 66:11745–11753. doi:10.1158/0008-5472.CAN-06-2322
Simon-Gracia L, Hunt H, Scodeller PD et al (2016) Paclitaxel-loaded polymersomes for enhanced intraperitoneal chemotherapy. Mol Cancer Ther 15:670–680. doi:10.1158/1535-7163.MCT-15-0713-T
Singha NC, Nekoroski T, Zhao C et al (2014) Tumor-associated hyaluronan limits efficacy of monoclonal antibody therapy. Mol Cancer Ther 14:523–532. doi:10.1158/1535-7163.MCT-14-0580
Slsca RF, Gkamt HHLAI, Tholqard JC (1971) Histochemical demonstration of acid mucopolysaccharide production by tissue cultured epithelial-like cells *. 181:173–181
St Croix B, Man S, Kerbel RS (1998) Reversal of intrinsic and acquired forms of drug resistance by hyaluronidase treatment of solid tumors. Cancer Lett 131:35–44, doi: S0304-3835(98)00199-2 [pii]
Stern R (2008) Hyaluronidases in cancer biology. Semin Cancer Biol 18:275–280. doi:10.1016/j.semcancer.2008.03.017
Stern R, Asari A, Sugahara K (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699–715. doi:10.1016/j.ejcb.2006.05.009
Sugahara K, Yamada S, Sugiura M et al (1992) Identification of the reaction products of the purified hyaluronidase from stonefish (Synanceja horrida) venom. Biochem J 283(Pt 1):99–104
Suwiwat S, Ricciardelli C, Tammi R et al (2004) Expression of extracellular matrix components versican, chondroitin sulfate, tenascin, and hyaluronan, and their association with disease outcome in node-negative breast cancer. Clin Cancer Res 10:2491–2498
Swyer G (1947) The hyaluronidase content of semen. Biochem J 41:409
Toole BP (2004) Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 4:528–539. doi:10.1038/nrc1391
Toole BP (2009) Hyaluronan-CD44 interactions in cancer: paradoxes and possibilities. Clin Cancer Res 15:7462–7468. doi:10.1158/1078-0432.CCR-09-0479
Turley EA, Tretiak M (1985) Glycosaminoglycan production by murine melanoma variants in vivo and in vitro. Cancer Res 45:5098–5105
Verzijl N, DeGroot J, Thorpe SR et al (2000) Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 275:39027–39031. doi:10.1074/jbc.M006700200
Wessels MR, Moses AE, Goldberg JB, DiCesare TJ (1991) Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci. Proc Natl Acad Sci U S A 88:8317–8321. doi:10.1073/pnas.88.19.8317
Whatcott CJ, Han H, Posner RG et al (2011) Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look. Cancer Discov 1:291–296. doi:10.1158/2159-8290.CD-11-0136
Wu C-C, Hu Y, Miller M et al (2015) Protection and delivery of anthelmintic protein Cry5B to nematodes using mesoporous silicon particles. ACS Nano 9:6158–6167. doi:10.1021/acsnano.5b01426
Zhang L, Underhill CB, Chen L (1995) Hyaluronan on the surface of tumor cells is correlated with metastatic behavior hyaluronan on the surface of tumor cells is correlated with metastatic behavior. Cancer Res 55:428–433
Zhou H, Fan Z, Deng J et al (2016) Hyaluronidase embedded in nanocarrier PEG shell for enhanced tumor penetration and highly efficient antitumor efficacy. Nano Lett 16:3268. doi:10.1021/acs.nanolett.6b00820, acs.nanolett.6b00820
Acknowledgements
The author would like to Patricia Scodeller for the graphic design, and Eduardo Scodeller, Matilde Bonder, and Lorena Simon-Gracia for their careful proofreading of this chapter.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Scodeller, P. (2016). Extracellular Matrix Degrading Enzymes for Nanocarrier-Based Anticancer Therapy. In: Prokop, A., Weissig, V. (eds) Intracellular Delivery III. Fundamental Biomedical Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-43525-1_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-43525-1_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-43523-7
Online ISBN: 978-3-319-43525-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)