The Metastatic Stage-dependent Mucosal Expression of Sialic Acid is a Potential Marker for Targeting Colon Cancer with Cationic Polymers
Tóm tắt
Locoregional recurrence is the most common complication after adenocarcinoma resection in the colon, despite adjuvant chemotherapy. Therapy efficacy could be improved if designed to target malignant cells by incorporating specific recognition factors in the drugs or the drug vehicles. The aim of this study was to elucidate whether the overexpression of sialic acid (SA) on colonic malignant tissues could be utilized for drug targeting by cationic polymers. Cell lines (IEC-6, SW-480 and SW-620) and colon polyps and normal adjacent tissues harvested from dimethylhydrazine (DMH) induced rats were used as in vitro and in vivo models of different metastatic stages of colon cancer. SA expression was identified by fluorescent wheat germ agglutinin (WGA), and verified by pretreatment with neuraminidase. The role of mucus in the mucosal binding experiments was explored by pretreatment with dithiothreitol (DTT). The binding of FITC labeled cationic polymers of various degrees of cationization to normal and malignant colonic cells and tissue was measured. SA was overexpressed on malignant colonic cells and tissues, and its expression correlated to the metastatic stage in vitro. The binding of the cationic copolymers to the cell lines and tissues correlated with the charge density of the polymer and with the metastatic stage of the cell line. The interaction between the malignant colonic cells and tissues with the polymers was SA dependent and increased after mucus removal. Cationic polymers could be used as a targeting tool to colonic malignant epithelium, to be implemented in drug delivery and diagnosis.
Tài liệu tham khảo
J. P. Arnoletti, and K. I. Bland. Neoadjuvant and adjuvant therapy for rectal cancer. Surg. Oncol. Clin. N. Am. 15:147–157 (2006).
A. B. Benson, 3rd. New approaches to the adjuvant therapy of colon cancer. Oncologist 11:973–980 (2006).
R. Duncan, M. J. Vicent, F. Greco, and R. I. Nicholson. Polymer-drug conjugates: towards a novel approach for the treatment of endocrine-related cancer. Endocr. Relat. Cancer 12(Suppl 1):S189–S199 (2005).
R. K. Jain. Transport of molecules, particles and cells in solid tumors. Ann. Rev. Biomed. Eng. 1:241–263 (1999).
A. Nori, and J. Kopecek. Intracellular targeting of polymer-bound drugs for cancer chemotherapy. Adv. Drug Deliv. Rev. 57:609–636 (2005).
A. K. Azab, M. Srebnik, V. Doviner, and A. Rubinstein. Targeting normal and neoplastic tissues in the rat jejunum and colon with boronated, cationized acrylamide copolymers. J. Control. Release 106:14–25 (2005).
S. S. Goldman, N. D. Volkow, J. Brodie, and E. S. Flamm. Putrescine metabolism in human brain tumors. J. Neurooncol. 4:23–29 (1986).
A. R. Holmberg, M. Wilchek, M. Marquez, J.-E. Westlin, J. Du, and S. Nilsson. Ion exchange tumor targeting: a new approach. Clin. Cancer Res. 5:3056s–3058s (1999).
N. D. Volkow, S. S. Goldman, E. S. Flamm, H. Cravioto, A. P. Wolf, and J. Brodie. Labeled putrescine as a probe in brain tumors. Science 221:673–675 (1983).
M. Xu, Q. R. Chen, D. Kumar, S. A. Stass, and A. J. Mixson. In vivo gene therapy with a cationic polymer markedly enhances the antitumor activity of antiangiogenic genes. Mol. Genet. Metab. 64:193–197 (1998).
C. R. Dass, and P. F. Choong. Targeting of small molecule anticancer drugs to the tumour and its vasculature using cationic liposomes: lessons from gene therapy. Cancer Cell Int. 6:17 (2006).
F. Dall’Olio, and D. Trere. Expression of alpha 2,6-sialylated sugar chains in normal and neoplastic colon tissues. Detection by digoxigenin-conjugated Sambucus nigra agglutinin. Eur. J. Histochem. 37:257–265 (1993).
M. J. Vierbuchen, W. Fruechtnicht, S. Brackrock, K. T. Krause, and T. J. Zienkiewicz. Quantitative lectin-histochemical and immunohistochemical studies on the occurrence of alpha(2,3)- and alpha(2,6)-linked sialic acid residues in colorectal carcinomas. Relation to clinicopathologic features. Cancer 76:727–35 (1995).
K. Yamashita, K. Fukushima, T. Sakiyama, F. Murata, M. Kuroki, and Y. Matsuoka. Expression of Sia alpha 2->6Gal beta 1->4GlcNAc residues on sugar chains of glycoproteins including carcinoembryonic antigens in human colon adenocarcinoma: applications of Trichosanthes japonica agglutinin I for early diagnosis. Cancer Res. 55:1675–1679 (1995).
P. Gessner, S. Riedl, A. Quentmaier, and W. Kemmner. Enhanced activity of CMP-neuAc:Gal beta 1-4GlcNAc:alpha 2,6-sialyltransferase in metastasizing human colorectal tumor tissue and serum of tumor patients. Cancer Lett. 75:143–149 (1993).
B. P. Peters, S. Ebisu, I. J. Goldstein, and M. Flashner. Interaction of wheat germ agglutinin with sialic acid. Biochemistry 18:5505–5511 (1979).
A. Varki. Sialic acids as ligands in recognition phenomena. Faseb J. 11:248–255 (1997).
F. Gabor, E. Bogner, A. Weissenboeck, and M. Wirth. The lectin-cell interaction and its implications to intestinal lectin-mediated drug delivery. Adv. Drug Deliv. Rev. 56:459–480 (2004).
J. M. Gilbert, E. M. Thompson, G. Slavin, and A. E. Kark. Chemotherapy of chemically-induced colorectal tumours. J. R. Soc. Med. 76:467–472 (1983).
J. D. Benson, Y. N. Chen, S. A. Cornell-Kennon, M. Dorsch, S. Kim, M. Leszczyniecka, W. R. Sellers, and C. Lengauer. Validating cancer drug targets. Nature 441:451–456 (2006).
U. Vanhoefer. Molecular mechanisms and targeting of colorectal cancer. Semin. Oncol. 32:7–10 (2005).
C. R. Dass. Improving anti-angiogenic therapy via selective delivery of cationic liposomes to tumour vasculature. Int. J. Pharm. 267:1–12 (2003).
M. Aubery, M. Reynier, M. Lopez, E. Ogier-Denis, J. Font, and F. Bardin. WGA binding to the surface of two autologous human melanoma cell lines: different expression of sialyl and N-acetylglucosaminyl residues. Cell Biol. Int. Rep. 14:275–286 (1990).
M. Szeverenyi, R. Osmers, W. Rath, W. Kuhn, and L. Lampe. Changes in binding capacity of sialic acid-specific lectins in the connective tissue of the uterine cervix during its physiological maturation. Acta Physiol. Hung. 82:3–13 (1994).
P. de Albuquerque Garcia Redondo, C. V. Nakamura, W. de Souza, and J. A. Morgado-Diaz. Differential expression of sialic acid and N-acetylgalactosamine residues on the cell surface of intestinal epithelial cells according to normal or metastatic potential. J. Histochem. Cytochem. 52:629–640 (2004).
K. Chadee, W. A. Petri, Jr., D. J. Innes, and J. I. Ravdin. Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica. J. Clin. Invest. 80:1245–1254 (1987).
T. A. Saldena, F. D. Saravi, O. R. Arrieta, L. M. Cincunegui, and G. E. Carra. Effect of dithiothreitol on mucus gel layer and electrophysiological properties in rat colon. Rev. Esp. Fisiol. 53:385–386 (1997).
R. B. Campbell, D. Fukumura, E. B. Brown, L. M. Mazzola, Y. Izumi, R. K. Jain, V. P. Torchilin, and L. L. Munn. Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. Cancer Res. 62:6831–6836 (2002).
S. K. Lai, D. E. O'Hanlon, S. Harrold, S. T. Man, Y. Y. Wang, R. Cone, and J. Hanes. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl. Acad. Sci. U. S. A. 104:1482–1487 (2007).
A. C. Alder, E. C. Hamilton, T. Anthony, and G. A. Sarosi, Jr. Cancer risk in endoscopically unresectable colon polyps. Am. J. Surg. 192:644–648 (2006).
M. Betes Ibanez, M. A. Munoz-Navas, J. M. Duque, R. Angos, E. Macias, J. C. Subtil, M. Herraiz, S. de la Riva, M. Delgado-Rodriguez, and M. A. Martinez-Gonzelez. Diagnostic value of distal colonic polyps for prediction of advanced proximal neoplasia in an average-risk population undergoing screening colonoscopy. Gastrointest. Endosc. 59:634–641 (2004).
L. F. Butterly, M. P. Chase, H. Pohl, and G. S. Fiarman. Prevalence of clinically important histology in small adenomas. Clin. Gastroenterol. Hepatol. 4:343–348 (2006).
I. C. Lawrance, C. Sherrington, and K. Murray. Poor correlation between clinical impression, the small colonic polyp and their neoplastic risk. J. Gastroenterol. Hepatol. 21:563–568 (2006).