The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice

Author:

Engle Dannielle D.12ORCID,Tiriac Hervé12ORCID,Rivera Keith D.1,Pommier Arnaud12ORCID,Whalen Sean3ORCID,Oni Tobiloba E.12ORCID,Alagesan Brinda12ORCID,Lee Eun Jung12,Yao Melissa A.12ORCID,Lucito Matthew S.12,Spielman Benjamin12,Da Silva Brandon12,Schoepfer Christina12,Wright Kevin12,Creighton Brianna12ORCID,Afinowicz Lauren12ORCID,Yu Kenneth H.45ORCID,Grützmann Robert6,Aust Daniela7ORCID,Gimotty Phyllis A.8,Pollard Katherine S.39,Hruban Ralph H.10ORCID,Goggins Michael G.1011ORCID,Pilarsky Christian6ORCID,Park Youngkyu12ORCID,Pappin Darryl J.1ORCID,Hollingsworth Michael A.12,Tuveson David A.12ORCID

Affiliation:

1. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

2. Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.

3. Gladstone Institutes, San Francisco, CA 94158, USA.

4. David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

5. Joan and Sanford I. Weill Medical College, Cornell University, New York, NY 10065, USA.

6. Department of Surgery, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.

7. Institute for Pathology, Universitätsklinikum Dresden, 01307 Dresden, Germany.

8. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA.

9. Department of Epidemiology and Biostatistics, Institute for Human Genetics, Quantitative Biology Institute, Institute for Computational Health Sciences, and Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA 94158, USA.

10. Sidney Kimmel Cancer Center, The Sol Goldman Pancreatic Cancer Research Center, and Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.

11. Departments of Medicine and Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.

12. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Abstract

Sweet bystander becomes a villain Patients with pancreatic cancer often have elevated blood levels of CA19-9, a carbohydrate antigen present on many proteins. CA19-9 is thus commonly used as a biomarker for diagnosing and monitoring disease progression. In a study of mice, Engle et al. found that CA19-9 may be more than an innocent bystander that marks the presence of pancreatic disease; it may play a causal role in disease (see the Perspective by Halbrook and Crawford). Transgenic mice expressing the human enzymes that add CA19-9 to proteins developed severe pancreatitis that could be reversed by treatment with CA19-9 antibodies. When the transgenic mice also harbored a Kras oncogene, they went on to develop pancreatic cancer. These unexpected observations suggest new avenues for the treatment of pancreatic disease. Science , this issue p. 1156 ; see also p. 1132

Funder

National Institutes of Health

Lustgarten Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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