HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

Nishizawa, Satoshi; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Takahashi, Akiko; Tamura, Yasuaki; Mori, Takashi; Kanaseki, Takayuki; Kamiguchi, Kenjiro; Asanuma, Hiroko; Morita, Rena; Sokolovskaya, Alice; Matsuzaki, Junichi; Yamada, Ryoichi; Fujii, Reona; Kampinga, Harm H.; Kondo, Toru; Hasegawa, Tadashi; Hara, Isao; Sato, Noriyuki

doi:10.1158/0008-5472.can-11-3062

Cited by 112 publications

(133 citation statements)

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“…SP analysis and flow cytometry analysis of OR7C1 were performed as described previously and as described in the Supplementary Materials and Methods (14,17).…”

Section: Sp Analysis and Flow Cytometry Analysis Of Or7c1mentioning

confidence: 99%

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Morita

Hirohashi

Torigoe

et al. 2016

Clinical Cancer Research

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Purpose: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.Experimental Design: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.Results: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.Conclusions: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. Ó2016 AACR.

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“…SP analysis and flow cytometry analysis of OR7C1 were performed as described previously and as described in the Supplementary Materials and Methods (14,17).…”

Section: Sp Analysis and Flow Cytometry Analysis Of Or7c1mentioning

confidence: 99%

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Morita

Hirohashi

Torigoe

et al. 2016

Clinical Cancer Research

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“…Previous studies have demonstrated that SPs within different cancer cells are less differentiated and have characteristics of stem/progenitor cells (7,16,21). In addition, it has been confirmed that SP cells in RCCs exhibit TIC characteristics (8,9,22). Fig.…”

Section: Fractionated Irradiated Cells Exhibit High Tumorigenicity Anmentioning

confidence: 62%

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response

Gao

et al. 2017

Oncology Letters

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Abstract. The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

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“…Moreover, the data presented by Liao et al [40] have shown that the host immune system is able to recognize and distinguish CSCs with ALDH1 phenotype from nonCSC cells. In addition to ALDH1, other cancer antigens were found to be preferentially expressed in CSCs: Cyclin A1 was reported in leukemic stem cells of acute myeloid leukemia whereas DNAJB8 was identified as novel cancer antigen in renal CSCs [56,57] . This specific expression of cancer antigens may enable us to target CSCs specifically.…”

Section: Csc-induced Immune Responsesmentioning

confidence: 99%

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

Méry¹

2016

WJSC

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Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

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HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

Cited by 112 publications

References 50 publications

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

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