title: Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2.
abstract: Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain AGR2 expression in a cohort of lymph node-positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not.
authors.affiliation: Department of Urology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.|Present address: University of California San Francisco Medical Center, San Francisco, CA, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Ho
authors.affiliation: Department of Urology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.|Present address: Singapore Polytechnic, Center for Biomedical & Life Sciences, Singapore.
authors.forename: Sue-Ing
authors.initials: SI
authors.lastname: Quek
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.affiliation: Department of Urology, University Hospital of Bern, Bern, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Seiler
authors.affiliation: Institute of Pathology, University Hospital of Bern, Bern, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Fleischmann
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Lora
authors.initials: L
authors.lastname: Bagryanova
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chia
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Alvin Y
authors.initials: AY
authors.lastname: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism*
chemical_list: C502296:AGR2 protein, human; D014408:Biomarkers, Tumor; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins
keywords: bladder cancer; secreted AGR2; subcellular localization; urine biomarker