Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.
Bottom Line: 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 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.
Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.Show MeSH
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Mentions: To evaluate the functions of DNAJB8 in HT29 cells, we established DNAJB8-overexpressed cells. We confirmed the overexpression of DNAJB8 mRNA using quantitative RT-PCR (Fig. 2a). Expression levels of the stem cell markers SOX2, LGR5 and POU5F1 were increased by 2.2-fold, 2.3-fold and 2.1-fold, respectively, in DNAJB8-overexpressed HT29 cells compared with the level in the control HT29 cells (Fig. 2a). The percentage of SP cells in DNAJB8-overexpressed HT29 cells was higher than that in control HT29 cells (Fig. 2b). To confirm the tumorigenicity in vivo of DNAJB8-overexpressed HT29 cells, we used a xenograft transplantation model. The DNAJB8-overexpressed HT29 cells showed higher tumor-initiating ability compared with HT29 control cells (Fig. 2c). A sphere formation assay was used to evaluate CSC/CIC-like features. DNAJB8-overexpressed HT29 cells showed higher sphere-forming ability than that of HT29 control cells (Fig. 2d), indicating that overexpression of DNAJB8 induced CSC/CIC properties.
Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.