Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 4/2015

01-12-2015 | Non-Thematic Review

Genetically engineered mucin mouse models for inflammation and cancer

Authors: Suhasini Joshi, Sushil Kumar, Sangeeta Bafna, Satyanarayana Rachagani, Kay-Uwe Wagner, Maneesh Jain, Surinder K. Batra

Published in: Cancer and Metastasis Reviews | Issue 4/2015

Login to get access

Abstract

Mucins are heavily O-glycosylated proteins primarily produced by glandular and ductal epithelial cells, either in membrane-tethered or secretory forms, for providing lubrication and protection from various exogenous and endogenous insults. However, recent studies have linked their aberrant overexpression with infection, inflammation, and cancer that underscores their importance in tissue homeostasis. In this review, we present current status of the existing mouse models that have been developed to gain insights into the functional role(s) of mucins under physiological and pathological conditions. Knockout mouse models for membrane-associated (Muc1 and Muc16) and secretory mucins (Muc2) have helped us to elucidate the role of mucins in providing effective and protective barrier functions against pathological threats, participation in disease progression, and improved our understanding of mucin interaction with biotic and abiotic environmental components. Emphasis is also given to available transgenic mouse models (MUC1 and MUC7), which has been exploited to understand the context-dependent regulation and therapeutic potential of human mucins during inflammation and cancer.
Literature
1.
Montagne, L., Piel, C., & Lalles, J. P. (2004). Effect of diet on mucin kinetics and composition: nutrition and health implications. Nutrition Reviews, 62, 105–114.PubMedCrossRef
2.
3.
Rachagani, S., Torres, M. P., Moniaux, N., & Batra, S. K. (2009). Current status of mucins in the diagnosis and therapy of cancer. Biofactors, 35, 509–527.PubMedCentralPubMedCrossRef
4.
Kaur, S., Kumar, S., Momi, N., Sasson, A. R., & Batra, S. K. (2013). Mucins in pancreatic cancer and its microenvironment. Nature Reviews Gastroenterol Hepatology, 10, 607–620.CrossRef
5.
Andrianifahanana, M., Moniaux, N., & Batra, S. K. (2006). Regulation of mucin expression: mechanistic aspects and implications for cancer and inflammatory diseases. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1765, 189–222.CrossRef
6.
Itoh, Y., Kamata-Sakurai, M., Denda-Nagai, K., Nagai, S., Tsuiji, M., Ishii-Schrade, K., et al. (2008). Identification and expression of human epiglycanin/MUC21: a novel transmembrane mucin. Glycobiology, 18, 74–83.PubMedCrossRef
7.
Buisine, M. P., Desreumaux, P., Leteurtre, E., Copin, M. C., Colombel, J. F., Porchet, N., et al. (2001). Mucin gene expression in intestinal epithelial cells in Crohn’s disease. Gut, 49, 544–551.PubMedCentralPubMedCrossRef
8.
Corfield, A. P., Myerscough, N., Longman, R., Sylvester, P., Arul, S., & Pignatelli, M. (2000). Mucins and mucosal protection in the gastrointestinal tract: new prospects for mucins in the pathology of gastrointestinal disease. Gut, 47, 589–594.PubMedCentralPubMedCrossRef
9.
Singh, A. P., Chauhan, S. C., Bafna, S., Johansson, S. L., Smith, L. M., Moniaux, N., et al. (2006). Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas. Prostate, 66, 421–429.PubMedCrossRef
10.
Mukhopadhyay, P., Lakshmanan, I., Ponnusamy, M. P., Chakraborty, S., Jain, M., Pai, P., et al. (2013). MUC4 overexpression augments cell migration and metastasis through EGFR family proteins in triple negative breast cancer cells. PLoS One, 8, e54455.PubMedCentralPubMedCrossRef
11.
Senapati, S., Chaturvedi, P., Sharma, P., Venkatraman, G., Meza, J. L., El-Rifai, W., et al. (2008). Deregulation of MUC4 in gastric adenocarcinoma: potential pathobiological implication in poorly differentiated non-signet ring cell type gastric cancer. British Journal of Cancer, 99, 949–956.PubMedCentralPubMedCrossRef
12.
Chauhan, S. C., Singh, A. P., Ruiz, F., Johansson, S. L., Jain, M., Smith, L. M., et al. (2006). Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125). Modern Pathology, 19, 1386–1394.PubMedCrossRef
13.
Chaturvedi, P., Singh, A. P., Moniaux, N., Senapati, S., Chakraborty, S., Meza, J. L., et al. (2007). MUC4 mucin potentiates pancreatic tumor cell proliferation, survival, and invasive properties and interferes with its interaction to extracellular matrix proteins. Molecular Cancer Research, 5, 309–320.PubMedCrossRef
14.
Chaturvedi, P., Singh, A. P., Chakraborty, S., Chauhan, S. C., Bafna, S., Meza, J. L., et al. (2008). MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. Cancer Research, 68, 2065–2070.PubMedCentralPubMedCrossRef
15.
Ponnusamy, M. P., Singh, A. P., Jain, M., Chakraborty, S., Moniaux, N., & Batra, S. K. (2008). MUC4 activates HER2 signalling and enhances the motility of human ovarian cancer cells. British Journal of Cancer, 99, 520–526.PubMedCentralPubMedCrossRef
16.
Singh, P. K., & Hollingsworth, M. A. (2006). Cell surface-associated mucins in signal transduction. Trends in Cell Biology, 16, 467–476.PubMedCrossRef
17.
Ahmad, R., Raina, D., Trivedi, V., Ren, J., Rajabi, H., Kharbanda, S., et al. (2007). MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF-kappaB signalling. Nature Cell Biology, 9, 1419–1427.PubMedCentralPubMedCrossRef
18.
Rachagani, S., Macha, M. A., Ponnusamy, M. P., Haridas, D., Kaur, S., Jain, M., et al. (2012). MUC4 potentiates invasion and metastasis of pancreatic cancer cells through stabilization of fibroblast growth factor receptor 1. Carcinogenesis, 33, 1953–1964.PubMedCentralPubMedCrossRef
19.
Kumar, S., Das, S., Rachagani, S., Kaur, S., Joshi, S., Johansson, S. L., et al. (2014). NCOA3-mediated upregulation of mucin expression via transcriptional and post-translational changes during the development of pancreatic cancer. Oncogene. doi:10.​1038/​onc.​2014.​409.
20.
Li, Y., Liu, D., Chen, D., Kharbanda, S., & Kufe, D. (2003). Human DF3/MUC1 carcinoma-associated protein functions as an oncogene. Oncogene, 22, 6107–6110.PubMedCentralPubMedCrossRef
21.
Moniaux, N., Chaturvedi, P., Varshney, G. C., Meza, J. L., Rodriguez-Sierra, J. F., Aubert, J. P., et al. (2007). Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells. British Journal of Cancer, 97, 345–357.PubMedCentralPubMedCrossRef
22.
Singh, A. P., Moniaux, N., Chauhan, S. C., Meza, J. L., & Batra, S. K. (2004). Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis. Cancer Research, 64, 622–630.PubMedCrossRef
23.
Tsutsumida, H., Swanson, B. J., Singh, P. K., Caffrey, T. C., Kitajima, S., Goto, M., et al. (2006). RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells. Clinical Cancer Research, 12, 2976–2987.PubMedCrossRef
24.
Qiu, W., & Su, G. H. (2013). Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis. Cancer Metastasis Review, 32, 83–107.CrossRef
25.
Li, Q., Ren, J., & Kufe, D. (2004). Interaction of human MUC1 and beta-catenin is regulated by Lck and ZAP-70 in activated Jurkat T cells. Biochemical and Biophysical Research Communications, 315, 471–476.PubMedCrossRef
26.
Poh, T. W., Bradley, J. M., Mukherjee, P., & Gendler, S. J. (2009). Lack of Muc1-regulated beta-catenin stability results in aberrant expansion of CD11b+Gr1+ myeloid-derived suppressor cells from the bone marrow. Cancer Research, 69, 3554–3562.PubMedCentralPubMedCrossRef
27.
Gu, H., Marth, J. D., Orban, P. C., Mossmann, H., & Rajewsky, K. (1994). Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science, 265, 103–106.PubMedCrossRef
28.
Long, D. P., Zhao, A. C., Chen, X. J., Zhang, Y., Lu, W. J., Guo, Q., et al. (2012). FLP recombinase-mediated site-specific recombination in silkworm, Bombyx mori. PLoS One. doi:10.​1371/​journal.​pone.​0040150.
29.
Shekels, L. L., & Ho, S. B. (2003). Characterization of the mouse Muc3 membrane bound intestinal mucin 5′ coding and promoter regions: regulation by inflammatory cytokines. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1627, 90–100.CrossRef
30.
Gum, J. R., Jr., Crawley, S. C., Hicks, J. W., Szymkowski, D. E., & Kim, Y. S. (2002). MUC17, a novel membrane-tethered mucin. Biochemical and Biophysical Research Communications, 291, 466–475.PubMedCrossRef
31.
Senapati, S., Das, S., & Batra, S. K. (2010). Mucin-interacting proteins: from function to therapeutics. Trends in Biochemical Sciences, 35, 236–245.PubMedCentralPubMedCrossRef
32.
Joshi, S., Kumar, S., Choudhury, A., Ponnusamy, M. P., & Batra, S. K. (2014). Altered mucins (MUC) trafficking in benign and malignant conditions. Oncotarget, 5, 7272–7284.PubMedCentralPubMedCrossRef
33.
Spicer, A. P., Parry, G., Patton, S., & Gendler, S. J. (1991). Molecular cloning and analysis of the mouse homologue of the tumor-associated mucin, MUC1, reveals conservation of potential O-glycosylation sites, transmembrane, and cytoplasmic domains and a loss of minisatellite-like polymorphism. Journal of Biological Chemistry, 266, 15099–15109.PubMed
34.
Shekels, L. L., Lyftogt, C., Kieliszewski, M., Filie, J. D., Kozak, C. A., & Ho, S. B. (1995). Mouse gastric mucin: cloning and chromosomal localization. Biochemical Journal, 311(Pt. 3), 775–785.PubMedCentralPubMedCrossRef
35.
Desseyn, J. L., Clavereau, I., & Laine, A. (2002). Cloning, chromosomal localization and characterization of the murine mucin gene orthologous to human MUC4. European Journal of Biochemistry, 269, 3150–3159.PubMedCrossRef
36.
Maeda, T., Inoue, M., Koshiba, S., Yabuki, T., Aoki, M., Nunokawa, E., et al. (2004). Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16). Journal of Biological Chemistry, 279, 13174–13182.PubMedCrossRef
37.
Goodell, C. A., Belisle, J. A., Gubbels, J. A., Migneault, M., Rancourt, C., Connor, J., et al. (2009). Characterization of the tumor marker muc16 (ca125) expressed by murine ovarian tumor cell lines and identification of a panel of cross-reactive monoclonal antibodies. Journal of Ovarian Research. doi:10.​1186/​1757-2215-2-8.PubMedCentralPubMed
38.
Dougherty, G. J., Kay, R. J., & Humphries, R. K. (1989). Molecular cloning of 114/A10, a cell surface antigen containing highly conserved repeated elements, which is expressed by murine hemopoietic progenitor cells and interleukin-3-dependent cell lines. Journal of Biological Chemistry, 264, 6509–6514.PubMed
39.
Williams, S. J., Wreschner, D. H., Tran, M., Eyre, H. J., Sutherland, G. R., & McGuckin, M. A. (2001). Muc13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells. Journal of Biological Chemistry, 276, 18327–18336.PubMedCrossRef
40.
Higuchi, T., Orita, T., Nakanishi, S., Katsuya, K., Watanabe, H., Yamasaki, Y., et al. (2004). Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney. Journal of Biological Chemistry, 279, 1968–1979.PubMedCrossRef
41.
Chen, Y., Zhao, Y. H., Kalaslavadi, T. B., Hamati, E., Nehrke, K., Le, A. D., et al. (2004). Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissues. American Journal of Respiratory Cell and Molecular Biology, 30, 155–165.PubMedCrossRef
42.
Desseyn, J. L., & Laine, A. (2003). Characterization of mouse muc6 and evidence of conservation of the gel-forming mucin gene cluster between human and mouse. Genomics, 81, 433–436.PubMedCrossRef
43.
Pigny, P., Guyonnet-Duperat, V., Hill, A. S., Pratt, W. S., Galiegue Zouitina, S., D’Hooge, M. C., et al. (1996). Human mucin genes assigned to 11p15.5: identification and organization of a cluster of genes. Genomics, 38, 340–352.PubMedCrossRef
44.
Johansson, M. E., Larsson, J. M., & Hansson, G. C. (2011). The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proceedings of the National Academy of Sciences of the United States of America, 108(Suppl 1), 4659–4665.PubMedCentralPubMedCrossRef
45.
Aslam, F., Palumbo, L., Augenlicht, L. H., & Velcich, A. (2001). The Sp family of transcription factors in the regulation of the human and mouse MUC2 gene promoters. Cancer Research, 61, 570–576.PubMed
46.
Van Klinken, B. J., Einerhand, A. W., Duits, L. A., Makkink, M. K., Tytgat, K. M., Renes, I. B., et al. (1999). Gastrointestinal expression and partial cDNA cloning of murine Muc2. Americal Journal of Physiology, 276, G115–G124.
47.
Inatomi, T., Tisdale, A. S., Zhan, Q., Spurr-Michaud, S., & Gipson, I. K. (1997). Cloning of rat Muc5AC mucin gene: comparison of its structure and tissue distribution to that of human and mouse homologues. Biochemical and Biophysical Research Communications, 236, 789–797.PubMedCrossRef
48.
Escande, F., Porchet, N., Aubert, J. P., & Buisine, M. P. (2002). The mouse Muc5b mucin gene: cDNA and genomic structures, chromosomal localization and expression. Biochemical Journal, 363, 589–598.PubMedCentralPubMedCrossRef
49.
Culp, D. J., Latchney, L. R., Fallon, M. A., Denny, P. A., Denny, P. C., Couwenhoven, R. I., et al. (2004). The gene encoding mouse Muc19: cDNA, genomic organization and relationship to Smgc. Physiological Genomics, 19, 303–318.PubMedCrossRef
50.
Toribara, N. W., Ho, S. B., Gum, E., Gum, J. R., Jr., Lau, P., & Kim, Y. S. (1997). The carboxyl-terminal sequence of the human secretory mucin, MUC6. Analysis of the primary amino acid sequence. Journal of Biological Chemistry, 272, 16398–16403.PubMedCrossRef
51.
Spicer, A. P., Rowse, G. J., Lidner, T. K., & Gendler, S. J. (1995). Delayed mammary tumor progression in Muc-1 null mice. Journal of Biological Chemistry, 270, 30093–30101.PubMedCrossRef
52.
Wang, H. H., Afdhal, N. H., Gendler, S. J., & Wang, D. Q. (2004). Targeted disruption of the murine mucin gene 1 decreases susceptibility to cholesterol gallstone formation. Journal of Lipid Research, 45, 438–447.PubMedCrossRef
53.
Parmley, R. R., & Gendler, S. J. (1998). Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus. Journal of Clinical Investigation, 102, 1798–1806.PubMedCentralPubMedCrossRef
54.
Besmer, D. M., Curry, J. M., Roy, L. D., Tinder, T. L., Sahraei, M., Schettini, J., et al. (2011). Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis. Cancer Research, 71, 4432–4442.PubMedCentralPubMedCrossRef
55.
56.
Nagaraj, S., Collazo, M., Corzo, C. A., Youn, J. I., Ortiz, M., Quiceno, D., et al. (2009). Regulatory myeloid suppressor cells in health and disease. Cancer Research, 69, 7503–7506.PubMedCentralPubMedCrossRef
57.
Linden, S. K., Sheng, Y. H., Every, A. L., Miles, K. M., Skoog, E. C., Florin, T. H., et al. (2009). MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy. PLoS Pathogens. doi:10.​1371/​journal.​ppat.​1000617.
58.
McGuckin, M. A., Every, A. L., Skene, C. D., Linden, S. K., Chionh, Y. T., Swierczak, A., et al. (2007). Muc1 mucin limits both Helicobacter pylori colonization of the murine gastric mucosa and associated gastritis. Gastroenterology, 133, 1210–1218.PubMedCrossRef
59.
Velcich, A., Yang, W., Heyer, J., Fragale, A., Nicholas, C., Viani, S., et al. (2002). Colorectal cancer in mice genetically deficient in the mucin Muc2. Science, 295, 1726–1729.PubMedCrossRef
60.
Yang, W., Velcich, A., Lozonschi, I., Liang, J., Nicholas, C., Zhuang, M., et al. (2005). Inactivation of p21WAF1/cip1 enhances intestinal tumor formation in Muc2-/- mice. American Journal of Pathology, 166, 1239–1246.PubMedCentralPubMedCrossRef
61.
Burger-van, P. N., van der Sluis, M., Bouma, J., Korteland-van Male, A. M., Lu, P., Van, S. I., et al. (2011). Colitis development during the suckling-weaning transition in mucin Muc2-deficient mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 301, G667–G678.CrossRef
62.
Lu, P., Burger-van, P. N., van der Sluis, M., Witte-Bouma, J., Kerckaert, J. P., van Goudoever, J. B., et al. (2011). Colonic gene expression patterns of mucin Muc2 knockout mice reveal various phases in colitis development. Inflammatory Bowel Diseases, 17, 2047–2057.PubMedCrossRef
63.
Moeeni, V., & Day, A. S. (2011). Impact of Inflammatory bowel disease upon growth in children and adolescents. International Scholarly Research Notices: Pediatrics, 2011, 365712.
64.
Van der Sluis, M., De Koning, B. A., De Bruijn, A. C., Velcich, A., Meijerink, J. P., Van Goudoever, J. B., et al. (2006). Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology, 131, 117–129.PubMedCrossRef
65.
Berg, D. J., Davidson, N., Kuhn, R., Muller, W., Menon, S., Holland, G., et al. (1996). Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. Journal of Clinical Investigation, 98, 1010–1020.PubMedCentralPubMedCrossRef
66.
Schwerbrock, N. M., Makkink, M. K., van der Sluis, M., Buller, H. A., Einerhand, A. W., Sartor, R. B., et al. (2004). Interleukin 10-deficient mice exhibit defective colonic Muc2 synthesis before and after induction of colitis by commensal bacteria. Inflammatory Bowel Diseases, 10, 811–823.PubMedCrossRef
67.
van der Sluis, M., Bouma, J., Vincent, A., Velcich, A., Carraway, K. L., Buller, H. A., et al. (2008). Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: mucin 2-interleukin 10-deficient mice. Laboratory Investigation, 88, 634–642.PubMedCrossRef
68.
Verburg, M., Renes, I. B., Meijer, H. P., Taminiau, J. A., Buller, H. A., Einerhand, A. W., et al. (2000). Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats. American Journal of Physiology-Gastrointestinal and Liver Physiology, 279, G1037–G1047.PubMed
69.
Guy-Grand, D., DiSanto, J. P., Henchoz, P., Malassis-Seris, M., & Vassalli, P. (1998). Small bowel enteropathy: role of intraepithelial lymphocytes and of cytokines (IL-12, IFN-gamma, TNF) in the induction of epithelial cell death and renewal. European Journal of Immunology, 28, 730–744.PubMedCrossRef
70.
Sellon, R. K., Tonkonogy, S., Schultz, M., Dieleman, L. A., Grenther, W., Balish, E., et al. (1998). Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infection and Immunity, 66, 5224–5231.PubMedCentralPubMed
71.
de Koning, B. A., Sluis, M., Lindenbergh-Kortleve, D. J., Velcich, A., Pieters, R., Buller, H. A., et al. (2007). Methotrexate-induced mucositis in mucin 2-deficient mice. Journal of Cellular Physiology, 210, 144–152.PubMedCrossRef
72.
73.
Hasnain, S. Z., Wang, H., Ghia, J. E., Haq, N., Deng, Y., Velcich, A., et al. (2010). Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection. Gastroenterology, 138, 1763–1771.PubMedCentralPubMedCrossRef
74.
75.
76.
Shimizu, A., Hirono, S., Tani, M., Kawai, M., Okada, K., Miyazawa, M., et al. (2012). Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma. Cancer Science, 103, 739–746.PubMedCrossRef
77.
Wang, Y., Cheon, D. J., Lu, Z., Cunningham, S. L., Chen, C. M., Luo, R. Z., et al. (2008). MUC16 expression during embryogenesis, in adult tissues, and ovarian cancer in the mouse. Differentiation, 76, 1081–1092.PubMedCentralPubMedCrossRef
78.
Lakshmanan, I., Ponnusamy, M. P., Das, S., Chakraborty, S., Haridas, D., Mukhopadhyay, P., et al. (2012). MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells. Oncogene, 31, 805–817.PubMedCentralPubMedCrossRef
79.
Peat, N., Gendler, S. J., Lalani, N., Duhig, T., & Taylor-Papadimitriou, J. (1992). Tissue-specific expression of a human polymorphic epithelial mucin (MUC1) in transgenic mice. Cancer Research, 52, 1954–1960.PubMed
80.
Schroeder, J. A., Thompson, M. C., Gardner, M. M., & Gendler, S. J. (2001). Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland. Journal of Biological Chemistry, 276, 13057–13064.PubMedCrossRef
81.
Schroeder, J. A., Masri, A. A., Adriance, M. C., Tessier, J. C., Kotlarczyk, K. L., Thompson, M. C., et al. (2004). MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. Oncogene, 23, 5739–5747.PubMedCrossRef
82.
Woo, J. K., Choi, Y., Oh, S. H., Jeong, J. H., Choi, D. H., Seo, H. S., et al. (2012). Mucin 1 enhances the tumor angiogenic response by activation of the AKT signaling pathway. Oncogene, 31, 2187–2198.PubMedCrossRef
83.
Beatty, P. L., Plevy, S. E., Sepulveda, A. R., & Finn, O. J. (2007). Cutting edge: transgenic expression of human MUC1 in IL-10-/- mice accelerates inflammatory bowel disease and progression to colon cancer. Journal of Immunology, 179, 735–739.CrossRef
84.
Tinder, T. L., Subramani, D. B., Basu, G. D., Bradley, J. M., Schettini, J., Million, A., et al. (2008). MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma. Journal of Immunology, 181, 3116–3125.CrossRef
85.
Rowse, G. J., Tempero, R. M., VanLith, M. L., Hollingsworth, M. A., & Gendler, S. J. (1998). Tolerance and immunity to MUC1 in a human MUC1 transgenic murine model. Cancer Research, 58, 315–321.PubMed
86.
Mukherjee, P., Ginardi, A. R., Madsen, C. S., Sterner, C. J., Adriance, M. C., Tevethia, M. J., et al. (2000). Mice with spontaneous pancreatic cancer naturally develop MUC-1-specific CTLs that eradicate tumors when adoptively transferred. Journal of Immunology, 165, 3451–3460.CrossRef
87.
Akporiaye, E. T., Bradley-Dunlop, D., Gendler, S. J., Mukherjee, P., Madsen, C. S., Hahn, T., et al. (2007). Characterization of the MUC1.Tg/MIN transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas. Vaccine, 25, 6965–6974.PubMedCentralPubMedCrossRef
88.
Lakshminarayanan, V., Thompson, P., Wolfert, M. A., Buskas, T., Bradley, J. M., Pathangey, L. B., et al. (2012). Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine. Proceedings of the National Academy of Sciences of the United States of America, 109, 261–266.PubMedCentralPubMedCrossRef
89.
Goydos, J. S., Elder, E., Whiteside, T. L., Finn, O. J., & Lotze, M. T. (1996). A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma. Journal of Surgical Research, 63, 298–304.PubMedCrossRef
90.
Karanikas, V., Hwang, L. A., Pearson, J., Ong, C. S., Apostolopoulos, V., Vaughan, H., et al. (1997). Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein. Journal of Clinical Investigation, 100, 2783–2792.PubMedCentralPubMedCrossRef
91.
Soares, M. M., Mehta, V., & Finn, O. J. (2001). Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection. Journal of Immunology, 166, 6555–6563.CrossRef
92.
Von Mensdorff-Pouilly, S., Petrakou, E., Kenemans, P., van Uffelen, K., Verstraeten, A. A., Snijdewint, F. G., et al. (2000). Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and n-acetylgalactosamine (GalNAc) peptides. International Journal of Cancer, 86, 702–712.CrossRef
93.
Dziadek, S., Griesinger, C., Kunz, H., & Reinscheid, U. M. (2006). Synthesis and structural model of an alpha (2,6)-sialyl-t glycosylated MUC1 eicosapeptide under physiological conditions. Chemistry, 12, 4981–4993.PubMedCrossRef
94.
Ninkovic, T., & Hanisch, F. G. (2007). O-glycosylated human MUC1 repeats are processed in vitro by immunoproteasomes. Journal of Immunology, 179, 2380–2388.CrossRef
95.
Turner, M. S., Cohen, P. A., & Finn, O. J. (2007). Lack of effective MUC1 tumor antigen-specific immunity in MUC1-transgenic mice results from a Th/T regulatory cell imbalance that can be corrected by adoptive transfer of wild-type Th cells. Journal of Immunology, 178, 2787–2793.CrossRef
96.
Beatty, P. L., Narayanan, S., Gariepy, J., Ranganathan, S., & Finn, O. J. (2010). Vaccine against MUC1 antigen expressed in inflammatory bowel disease and cancer lessens colonic inflammation and prevents progression to colitis-associated colon cancer. Cancer Prevention Research (Philadelphia), 3, 438–446.CrossRef
97.
Ehre, C., Worthington, E. N., Liesman, R. M., Grubb, B. R., Barbier, D., O’Neal, W. K., et al. (2012). Overexpressing mouse model demonstrates the protective role of Muc5ac in the lungs. Proceedings of the National Academy of Sciences of the United States of America, 109, 16528–16533.PubMedCentralPubMedCrossRef
98.
Li, S., Intini, G., & Bobek, L. A. (2006). Modulation of MUC7 mucin expression by exogenous factors in airway cells in vitro and in vivo. American Journal of Respiratory Cell and Molecular Biology, 35, 95–102.
99.
Bobek, L. A., Tsai, H., Biesbrock, A. R., & Levine, M. J. (1993). Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7). Journal of Biological Chemistry, 268, 20563–20569.PubMed
100.
Bobek, L. A., Li, H., Rojstaczer, N., Jones, C., Gross, K. W., & Levine, M. J. (1998). Tissue-specific expression of human salivary mucin gene, MUC7, in transgenic mice. Transgenic Research, 7, 195–204.PubMedCrossRef
101.
Biesbrock, A. R., Bobek, L. A., & Levine, M. J. (1997). MUC7 gene expression and genetic polymorphism. Glycoconjugate Journal, 14, 415–422.PubMedCrossRef
102.
Fan, H., & Bobek, L. A. (2010). Regulation of human MUC7 mucin gene expression by cigarette smoke extract or cigarette smoke and Pseudomonas aeruginosa lipopolysaccharide in human airway epithelial cells and in MUC7 transgenic mice. Open Respiratory Medicine Journal, 4, 63–70.PubMedCentralPubMed
103.
Rachagani, S., Torres, M. P., Kumar, S., Haridas, D., Baine, M., Macha, M. A., et al. (2012). Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy. Journal of Hematology & Oncology, 5, 68.CrossRef
104.
Tian, H., Zhou, Q., Lasonos, A., Spriggs DR. (2013). Overexpression of the carboxyl-terminus of MUC16 can accelerate the occurrence of phenotypes in p53 heterozygous mouse model. Cancer Research, 73(8 Suppl). doi:10.​1158/​1538-7445.​AM2013-326.
105.
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001). Stem cells, cancer, and cancer. Nature, 414(6859), 105–111.PubMedCrossRef
106.
107.
108.
Ponnusamy, M. P., Seshacharyulu, P., Vaz, A., Dey, P., & Batra, S. K. (2011). MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells. Journal of Ovarian Research. doi:10.​1186/​1757-2215-4-7.PubMedCentralPubMed
109.
Sugiura, D., Denda Nagai, K., Takashima, M., Murakami, R., Nagai, S., Takeda, K., et al. (2012). Local effects of regulatory T cells in MUC1 transgenic mice potentiate growth of MUC1 expressing tumor cells in vivo.8 PLoS One. doi:10.​1371/​journal.​pone.​0044770.
110.
Tsai, C. J., Herrera-Goepfert, R., Tibshirani, R. J., Yang, S., Mohar, A., Guarner, J., et al. (2006). Changes of gene expression in gastric preneoplasia following Helicobacter pylori eradication therapy. Cancer Epidemiology, Biomarkers & Prevention, 15, 272–280.CrossRef
111.
Shimamura, T., Ito, H., Shibahara, J., Watanabe, A., Hippo, Y., Taniguchi, H., et al. (2005). Overexpression of MUC13 is associated with intestinal-type gastric cancer. Cancer Science, 96, 265–273.PubMedCrossRef
112.
Munro, E. G., Jain, M., Oliva, E., Kamal, N., Lele, S. M., Lynch, M. P., et al. (2009). Upregulation of MUC4 in cervical squamous cell carcinoma: pathologic significance. International Journal of Gynecological Pathology, 28, 127–133.PubMedCentralPubMedCrossRef
113.
Shibahara, H., Tamada, S., Higashi, M., Goto, M., Batra, S. K., Hollingsworth, M. A., et al. (2004). MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type. Hepatology, 39, 220–229.PubMedCrossRef
114.
Chung, M. H., Choi, J. Y., Lee, W. S., Kim, H. N., & Yoon, J. H. (2002). Compositional difference in middle ear effusion: mucous versus serous. Laryngoscope, 112, 152–155.PubMedCrossRef
115.
Yuta, A., Ali, M., Sabol, M., Gaumond, E., & Baraniuk, J. N. (1997). Mucoglycoprotein hypersecretion in allergic rhinitis and cystic fibrosis. American Journal of Physiology, 273, L1203–L1207.PubMed
116.
Vinall, L. E., King, M., Novelli, M., Green, C. A., Daniels, G., Hilkens, J., et al. (2002). Altered expression and allelic association of the hypervariable membrane mucin MUC1 in Helicobacter pylori gastritis. Gastroenterology, 123, 41–49.PubMedCrossRef
117.
Kirkbride, H. J., Bolscher, J. G., Nazmi, K., Vinall, L. E., Nash, M. W., Moss, F. M., et al. (2001). Genetic polymorphism of MUC7: allele frequencies and association with asthma. European Journal of Human Genetics, 9, 347–354.PubMedCrossRef
118.
Watson, A. M., Ngor, W. M., Gordish-Dressman, H., Freishtat, R. J., & Rose, M. C. (2009). MUC7 polymorphisms are associated with a decreased risk of a diagnosis of asthma in an African American population. Journal of Investigative Medicine, 57, 882–886.PubMedCentralPubMed
119.
Carrara, S., Cangi, M. G., Arcidiacono, P. G., Perri, F., Petrone, M. C., Mezzi, G., et al. (2011). Mucin expression pattern in pancreatic diseases: findings from EUS-guided fine-needle aspiration biopsies. American Journal of Gastroenterology, 106, 1359–1363.PubMedCrossRef
120.
Retz, M., Lehmann, J., Roder, C., Plotz, B., Harder, J., Eggers, J., et al. (1998). Differential mucin MUC7 gene expression in invasive bladder carcinoma in contrast to uniform MUC1 and MUC2 gene expression in both normal urothelium and bladder carcinoma. Cancer Research, 58, 5662–5666.PubMed
Metadata
Title
Genetically engineered mucin mouse models for inflammation and cancer
Authors
Suhasini Joshi
Sushil Kumar
Sangeeta Bafna
Satyanarayana Rachagani
Kay-Uwe Wagner
Maneesh Jain
Surinder K. Batra
Publication date
01-12-2015
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 4/2015
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-015-9549-1

Other articles of this Issue 4/2015

Cancer and Metastasis Reviews 4/2015 Go to the issue

NON-THEMATIC REVIEW

Urothelial cancer stem cells and epithelial plasticity: current concepts and therapeutic implications in bladder cancer

CLINICAL

New advances in ovarian autotransplantation to restore fertility in cancer patients

NON-THEMATIC REVIEW

The origin of prostate metastases: emerging insights

Non-Thematic Review

Expression of estrogen and progesterone receptors across human malignancies: new therapeutic opportunities

Non-Thematic Review

Contribution of very late antigen-4 (VLA-4) integrin to cancer progression and metastasis

NON-THEMATIC REVIEW

Protease-activated receptors (PARs)—biology and role in cancer invasion and metastasis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits