Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells

Ryuji Matsumoto, Masumi Tsuda, Kazuhiko Yoshida, Mishie Tanino, Taichi Kimura, Hiroshi Nishihara, Takashige Abe, Nobuo Shinohara, Katsuya Nonomura, Shinya Tanaka

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.

Original languageEnglish
Article number34625
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Oct 4
Externally publishedYes

Fingerprint

Interleukin-1
Drug Resistance
Urinary Bladder Neoplasms
Neoplasm Metastasis
Neoplasms
Flufenamic Acid
Cell Line
Gastropoda
carbonyl reductase (NADPH)
Microarray Analysis
Heterografts
Cisplatin
Anti-Inflammatory Agents
Cytokines
Bone and Bones
Lung
Survival
Liver
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells. / Matsumoto, Ryuji; Tsuda, Masumi; Yoshida, Kazuhiko; Tanino, Mishie; Kimura, Taichi; Nishihara, Hiroshi; Abe, Takashige; Shinohara, Nobuo; Nonomura, Katsuya; Tanaka, Shinya.

In: Scientific reports, Vol. 6, 34625, 04.10.2016.

Research output: Contribution to journalArticle

Matsumoto, Ryuji ; Tsuda, Masumi ; Yoshida, Kazuhiko ; Tanino, Mishie ; Kimura, Taichi ; Nishihara, Hiroshi ; Abe, Takashige ; Shinohara, Nobuo ; Nonomura, Katsuya ; Tanaka, Shinya. / Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells. In: Scientific reports. 2016 ; Vol. 6.
@article{9f50df5e088341028c5be54b88bf7186,
title = "Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells",
abstract = "In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.",
author = "Ryuji Matsumoto and Masumi Tsuda and Kazuhiko Yoshida and Mishie Tanino and Taichi Kimura and Hiroshi Nishihara and Takashige Abe and Nobuo Shinohara and Katsuya Nonomura and Shinya Tanaka",
year = "2016",
month = "10",
day = "4",
doi = "10.1038/srep34625",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells

AU - Matsumoto, Ryuji

AU - Tsuda, Masumi

AU - Yoshida, Kazuhiko

AU - Tanino, Mishie

AU - Kimura, Taichi

AU - Nishihara, Hiroshi

AU - Abe, Takashige

AU - Shinohara, Nobuo

AU - Nonomura, Katsuya

AU - Tanaka, Shinya

PY - 2016/10/4

Y1 - 2016/10/4

N2 - In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.

AB - In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.

UR - http://www.scopus.com/inward/record.url?scp=84989903290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989903290&partnerID=8YFLogxK

U2 - 10.1038/srep34625

DO - 10.1038/srep34625

M3 - Article

C2 - 27698389

AN - SCOPUS:84989903290

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 34625

ER -