Heat Shock Protein DNAJB8 is a Novel Target for Immunotherapy of Colon Cancer-initiating Cells

Overview

Journal Cancer Sci

Specialty Oncology

Date 2014 Jan 24

PMID 24450541

Citations 36

Authors

Rena Morita

Satoshi Nishizawa

Toshihiko Torigoe

Akari Takahashi

Yasuaki Tamura

Tomohide Tsukahara

Takayuki Kanaseki

Alice Sokolovskaya

Vitaly Kochin

Toru Kondo

Satoshi Hashino

Masahiro Asaka

Isao Hara

Yoshihiko Hirohashi

Noriyuki Sato

Affiliations

Soon will be listed here.

Abstract

The aim of the present study was to establish cancer stem-like cell/cancer-initiating cell (CSC/CIC)-targeting immunotherapy. The CSC/CIC are thought to be essential for tumor maintenance, recurrence and distant metastasis. Therefore they are reasonable targets for cancer therapy. In the present study, we found that a heat shock protein (HSP) 40 family member, DnaJ (Hsp40) homolog, subfamily B, member 8 (DNAJB8), is preferentially expressed in CSC/CIC derived from colorectal cancer (CRC) cells rather than in non-CSC/CIC. Overexpression of DNAJB8 enhanced the expression of stem cell markers and tumorigenicity, indicating that DNAJB8 has a role in CRC CSC/CIC. A DNAJB8-specific cytotoxic T lymphocyte (CTL) response could be induced by a DNAJB8-derived antigenic peptide. A CTL clone specific for DNAJB8 peptide showed higher killing activity to CRC CSC/CIC compared with non-CSC/CIC, and CTL adoptive transfer into CRC CSC/CIC showed an antitumor effect in vivo. Taken together, the results indicate that DNAJB8 is expressed and has role in CRC CSC/CIC and that DNAJB8 is a novel target of CRC CSC/CIC-targeting immunotherapy.

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