Establishment of an antibody specific for cancer-associated haptoglobin: a possible implication of clinical investigation

Oncotarget 9 巻 16 号 12732-12744 頁 2018-01-29 発行
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タイトル ( eng )
Establishment of an antibody specific for cancer-associated haptoglobin: a possible implication of clinical investigation
作成者
Nishino Kimihiro
Koda Sayaka
Kataoka Naoya
Takamatsu Shinji
Ikeda Shun
Kamamatsu Yuka
Morishita Koichi
Moriwaki Kenta
Eguchi Hidetoshi
Yamamoto Eiko
Kikkawa Fumitaka
Tomita Yasuhiko
Kamada Yoshihiro
Miyoshi Eiji
収録物名
Oncotarget
9
16
開始ページ 12732
終了ページ 12744
抄録
We previously found that the serum level of fucosylated haptoglobin (Fuc-Hpt) was significantly increased in pancreatic cancer patients. To delineate the mechanism underlying this increase and develop a simple detection method, we set out to generate a monoclonal antibody (mAb) specific for Fuc-Hpt. After multiple screenings by enzyme-linked immunosorbent assay (ELISA), a 10-7G mAb was identified as being highly specific for Fuc-Hpt generated in a cell line as well as for Hpt derived from a pancreatic cancer patient. As a result from affinity chromatography with 10-7G mAb, followed by lectin blot and mass spectrometry analyses, it was found that 10-7G mAb predominantly recognized both Fuc-Hpt and prohaptoglobin (proHpt), which was also fucosylated. In immunohistochemical analyses, hepatocytes surrounding metastasized cancer cells were stained by the 10-7G mAb, but neither the original cancer cells themselves nor normal hepatocytes exhibited positive staining, suggesting that metastasized cancer cells promote Fuc-Hpt production in adjacent hepatocytes. Serum level of Fuc-Hpt determined with newly developed ELISA system using the 10-7G mAb, was increased in patients of pancreatic and colorectal cancer. Interestingly, dramatic increases in Fuc-Hpt levels were observed at the stage IV of colorectal cancer. These results indicate that the 10-7G mAb developed is a promising antibody which recognizes Fuc-Hpt and could be a useful diagnostic tool for detecting liver metastasis of cancer.
著者キーワード
fucosylation
glycosylation
haptoglobin
glycan antibody
cancer biomarker
内容記述
This study was performed as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan and was supported by JSPS KAKENHI Grant Number JP16H05226.
言語
英語
資源タイプ 学術雑誌論文
出版者
Impact Journals
発行日 2018-01-29
権利情報
Copyright (c) 2018 Nishino et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
出版タイプ Version of Record(出版社版。早期公開を含む)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 1949-2553
[DOI] 10.18632/oncotarget.24332
[PMID] 29560105
[DOI] https://doi.org/10.18632/oncotarget.24332