Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2.

Ho, Melissa E; Quek, Sue-Ing; True, Lawrence D; Seiler, Roland; Fleischmann, Achim; Bagryanova, Lora; Kim, Sara R; Chia, David; Goodglick, Lee; Shimizu, Yoshiko; Rosser, Charles J; Gao, Yuqian; Liu, Alvin Y (2016). Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2. OncoTarget, 7(13), pp. 15747-15756. Impact Journals LLC 10.18632/oncotarget.7400

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Seiler, Roland and Fleischmann, Achim

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Ekkehard Hewer

Date Deposited:

15 Feb 2017 14:37

Last Modified:

15 Feb 2017 14:37

Publisher DOI:

10.18632/oncotarget.7400

PubMed ID:

26894971

Uncontrolled Keywords:

bladder cancer; secreted AGR2; subcellular localization; urine biomarker

BORIS DOI:

10.7892/boris.95900

URI:

https://boris.unibe.ch/id/eprint/95900

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