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Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.

Morita R, Nishizawa S, Torigoe T, Takahashi A, Tamura Y, Tsukahara T, Kanaseki T, Sokolovskaya A, Kochin V, Kondo T, Hashino S, Asaka M, Hara I, Hirohashi Y, Sato N - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

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DNAJB8 peptides carrying a HLA-A24 binding motif. (a) Candidate of DNAJB8 peptides carrying a HLA-A24 binding motif. (b) Peptide-binding assay. Binding affinity was evaluated by comparing mean fluorescence intensity of HLA-A24 expression in the presence of peptide pulsation to mean fluorescence intensity in the absence of the peptide. Survivin-2B_80(9) (AYACNTSTL) peptide was used as a positive control and SL8C (SIINFEKL) peptide was used as a negative control.
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fig03: DNAJB8 peptides carrying a HLA-A24 binding motif. (a) Candidate of DNAJB8 peptides carrying a HLA-A24 binding motif. (b) Peptide-binding assay. Binding affinity was evaluated by comparing mean fluorescence intensity of HLA-A24 expression in the presence of peptide pulsation to mean fluorescence intensity in the absence of the peptide. Survivin-2B_80(9) (AYACNTSTL) peptide was used as a positive control and SL8C (SIINFEKL) peptide was used as a negative control.

Mentions: To verify the immunogenicity for peptides from DNAJB8 protein, DNAJB8-specific CTL were induced using HLA-A*2402-positive healthy volunteer donors. Candidate antigenic peptides carrying the HLA-A*2402-binding anchor motif were screened according to the amino acid sequence of DNAJB8 protein and there were four candidate peptides (DNAJB8_22[8], DNAJB8_90[10], DNAJB8_99[9] and DNAJB8_143[9]) (Fig. 3). The HLA-A24 binding ability was then assessed using a HLA-A24 binding assay with SL8C peptide as a negative control and Survivin-2B_80(9) as a positive control. DNAJB8_22(9), DNAJB8_99(9) and DNAJB8_143(9) showed ability to bind to HLA-A24, whereas DNAJB8_90(10) did not (Fig. 3). Therefore, DNAJB8_22(9), DNAJB8_99(9) and DNAJB8_143(9) peptides were used for further CTL induction experiments.


Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.

Morita R, Nishizawa S, Torigoe T, Takahashi A, Tamura Y, Tsukahara T, Kanaseki T, Sokolovskaya A, Kochin V, Kondo T, Hashino S, Asaka M, Hara I, Hirohashi Y, Sato N - Cancer Sci. (2014)

DNAJB8 peptides carrying a HLA-A24 binding motif. (a) Candidate of DNAJB8 peptides carrying a HLA-A24 binding motif. (b) Peptide-binding assay. Binding affinity was evaluated by comparing mean fluorescence intensity of HLA-A24 expression in the presence of peptide pulsation to mean fluorescence intensity in the absence of the peptide. Survivin-2B_80(9) (AYACNTSTL) peptide was used as a positive control and SL8C (SIINFEKL) peptide was used as a negative control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317808&req=5

fig03: DNAJB8 peptides carrying a HLA-A24 binding motif. (a) Candidate of DNAJB8 peptides carrying a HLA-A24 binding motif. (b) Peptide-binding assay. Binding affinity was evaluated by comparing mean fluorescence intensity of HLA-A24 expression in the presence of peptide pulsation to mean fluorescence intensity in the absence of the peptide. Survivin-2B_80(9) (AYACNTSTL) peptide was used as a positive control and SL8C (SIINFEKL) peptide was used as a negative control.
Mentions: To verify the immunogenicity for peptides from DNAJB8 protein, DNAJB8-specific CTL were induced using HLA-A*2402-positive healthy volunteer donors. Candidate antigenic peptides carrying the HLA-A*2402-binding anchor motif were screened according to the amino acid sequence of DNAJB8 protein and there were four candidate peptides (DNAJB8_22[8], DNAJB8_90[10], DNAJB8_99[9] and DNAJB8_143[9]) (Fig. 3). The HLA-A24 binding ability was then assessed using a HLA-A24 binding assay with SL8C peptide as a negative control and Survivin-2B_80(9) as a positive control. DNAJB8_22(9), DNAJB8_99(9) and DNAJB8_143(9) showed ability to bind to HLA-A24, whereas DNAJB8_90(10) did not (Fig. 3). Therefore, DNAJB8_22(9), DNAJB8_99(9) and DNAJB8_143(9) peptides were used for further CTL induction experiments.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Show MeSH
Related in: MedlinePlus