52
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      MUC1 Selectively Targets Human Pancreatic Cancer in Orthotopic Nude Mouse Models

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2) antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

          Related collections

          Most cited references29

          • Record: found
          • Abstract: found
          • Article: not found

          Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells.

          Mucins (MUC) are high molecular weight O-linked glycoproteins whose primary functions are to hydrate, protect, and lubricate the epithelial luminal surfaces of the ducts within the human body. The MUC family is comprised of large secreted gel forming and transmembrane (TM) mucins. MUC1, MUC4, and MUC16 are the well-characterized TM mucins and have been shown to be aberrantly overexpressed in various malignancies including cystic fibrosis, asthma, and cancer. Recent studies have uncovered the unique roles of these mucins in the pathogenesis of cancer. These mucins possess specific domains that can make complex associations with various signaling pathways, impacting cell survival through alterations of cell growth, proliferation, death, and autophagy. The cytoplasmic domain of MUC1 serves as a scaffold for interaction with various signaling proteins. On the other hand, MUC4 mediates its effect by stabilizing and enhancing the activity of growth factor receptor ErbB2. MUC16, previously known as CA125, is a well-known serum marker for the diagnosis of ovarian cancer and has a key role in stimulation and dissemination of ovarian cancer cells by interacting with mesothelin and galectin. Therefore, herein we discuss the function and divergent mechanisms of MUC1, MUC4, and MUC16 in carcinogenesis in the context of alteration in cell growth and survival.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Establishment of a continuous tumor-cell line (panc-1) from a human carcinoma of the exocrine pancreas.

            An epithelioid cell line, started from a human pancreatic carcinoma of ductal cell origin, has been maintained in culture for over 2 years and has been subcultured more than 40 times. The PANC-1 cell line has a doubling time of 52 h and G6PD activity of the slow mobility of B type. Chromosome studies show a modal number of 63 with three distinct marker chromosomes and a small ring chromosome. The malignant nature of the PANC-1 cell line was verified by: (1) the ready growth of PANC-1 cells in soft agar and on top of a fibroblast monolayer; and (2) the formation of a progressively growing anaplastic carcinoma after injection of a nude-athymic mouse with PANC-1 cells.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              MUC1, the renaissance molecule.

              MUC1 is a large, heavily glycosylated mucin expressed on the apical surfaces of most simple, secretory epithelia including the mammary gland, gastrointestinal, respiratory, urinary and reproductive tracts. Although MUC1 was thought to be an epithelial-specific protein, it is now known to be expressed on a variety of hematopoietic cells as well. Mucins function in protection and lubrication of epithelial surfaces. Transmembrane mucins, which contain cytoplasmic tail domains, appear to have additional functions through their abilities to interact with many proteins involved in signal transduction and cell adhesion. The goal of this review is to highlight recent discoveries that suggest that MUC1 may be a multifunctional protein, located on the surfaces of cells as a sensor of the environment, poised to signal to the interior when things go awry.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 March 2015
                2015
                : 10
                : 3
                : e0122100
                Affiliations
                [1 ]Department of Surgery, University of California San Diego, San Diego, California, United States of America
                [2 ]AntiCancer, Inc., San Diego, California, United States of America
                [3 ]Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
                [4 ]Department of Surgery, Yokohama City University Graduate School of Medicine, Yokohama City, Japan
                [5 ]Surgical Service, VA San Diego Healthcare System, San Diego, California, United States of America
                National Cancer Institute, UNITED STATES
                Author notes

                Competing Interests: JYP, YH and RMH are non-salaried affiliates of AntiCancer Inc. AntiCancer Inc. markets animal models of cancer. There are no other competing interests. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

                Conceived and designed the experiments: JYP YH JYL AAM RMH MB. Performed the experiments: JYP YH JYL AAM. Analyzed the data: JYP JYL RMH MB. Contributed reagents/materials/analysis tools: JYP JYL RMH MB. Wrote the paper: JYP RMH MB.

                Article
                PONE-D-15-01493
                10.1371/journal.pone.0122100
                4376872
                25815753
                b4668870-cbf6-4216-b160-0874423877dc

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

                History
                : 14 January 2015
                : 18 February 2015
                Page count
                Figures: 4, Tables: 0, Pages: 10
                Funding
                This study was supported by grants from the National Cancer Institute CA142669 and CA132971 (to MB and AntiCancer, Inc.), and a grant from the Korea Research Foundation under the basic research promotion fund of the Ministry of Education and Health Resources Development of Korea 2010-0022990 (to JYP). The funder provided support in the form of salaries for authors [MB], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article