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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. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, 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. The blood proteomes also contain no significant peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained 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 urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition tomore » secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [5];  [5];  [5];  [5];  [6];  [6];  [7];  [3]
  1. Univ. of Washington, Seattle, WA (United States); Univ. of California San Francisco Medical Center, San Francisco, CA (United States)
  2. Univ. of Washington, Seattle, WA (United States); Singapore Polytechnic (Singapore)
  3. Univ. of Washington, Seattle, WA (United States)
  4. Univ. Hospital of Bern, Bern (Switzerland)
  5. Univ. of California, Los Angeles, CA (United States)
  6. Univ. of Hawaii, Honolulu, HI (United States)
  7. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1337234
Report Number(s):
PNNL-SA-114369
Journal ID: ISSN 1949-2553; 453040220
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Oncotarget
Additional Journal Information:
Journal Volume: 7; Journal Issue: 13; Journal ID: ISSN 1949-2553
Publisher:
Impact Journals
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; secreted AGR2; bladder cancer; subcellular localization; urine biomarker

Citation Formats

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, and Liu, Alvin Y. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2. United States: N. p., 2016. Web. doi:10.18632/oncotarget.7400.
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. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2. United States. doi:10.18632/oncotarget.7400.
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, and Liu, Alvin Y. Mon . "Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2". United States. doi:10.18632/oncotarget.7400. https://www.osti.gov/servlets/purl/1337234.
@article{osti_1337234,
title = {Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2},
author = {Ho, Melissa E. and Quek, Sue -Ing and True, Lawrence D. and Seiler, Roland and Fleischmann, Achim and Bagryanova, Lora and Kim, Sara R. and Chia, David and Goodglick, Lee and Shimizu, Yoshiko and Rosser, Charles J. and Gao, Yuqian and Liu, Alvin Y.},
abstractNote = {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. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, 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. The blood proteomes also contain no significant peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained 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 urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.},
doi = {10.18632/oncotarget.7400},
journal = {Oncotarget},
number = 13,
volume = 7,
place = {United States},
year = {2016},
month = {2}
}

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