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

Nishino Kimihiro

Koda Sayaka

Kataoka Naoya

Takamatsu Shinji

Nakano Miyako

Ikeda Shun

Kamamatsu Yuka

Morishita Koichi

Moriwaki Kenta

Eguchi Hidetoshi

Yamamoto Eiko

Kikkawa Fumitaka

Tomita Yasuhiko

Kamada Yoshihiro

Miyoshi Eiji

Oncotarget

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.

fucosylation

glycosylation

haptoglobin

glycan antibody

cancer biomarker

eng

Impact Journals

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.

[ISSN] 1949-2553

[DOI] 10.18632/oncotarget.24332

[PMID] 29560105

[DOI] https://doi.org/10.18632/oncotarget.24332