HSP60 may Predict Good Pathological Response to Neoadjuvant Chemoradiotherapy in Bladder Cancer

Urushibara, Masayasu; Kageyama, Yukio; Akashi, Takumi; Otsuka, Yukihiro; Takizawa, Touichiro; Koike, Masato; Kihara, Kazunori

doi:10.1093/jjco/hyl121

Cited by 28 publications

(14 citation statements)

References 16 publications

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“…Kamada et al (19) reported that Hsp27 knockdown inhibited tumor growth and enhanced sensitivity to chemotherapy in UMUC-3 human bladder cancer cells. Urushibara et al (20) reported that Hsp60 expression was associated with a good pathological response to neoadjuvant chemoradiotherapy. However, Syrigos et al (21) reported that Hsp70 expression was correlated with tumor grade, stage and overall survival.…”

Section: Discussionmentioning

confidence: 99%

High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy

Kawai

Enomoto

Morikawa

et al. 2013

Molecular and Clinical Oncology

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Abstract. Heat shock protein 105 (Hsp105) is one of the cancer/testis antigens, which is overexpressed in a variety of cancer cells, including urinary bladder cancer, and has been investigated as a target molecule for immunotherapy due to its immunogenicity. In this study, we assessed the expression of Hsp105 in primary bladder cancer samples from 84 patients treated with radical cystectomy, using immunohistochemical analysis, and investigated its correlation with clinicopathological characteristics and cancer-specific survival. The immunoreactivity of Hsp105 expression was evaluated as a score of 0-3, according to the intensity of the signal. The Hsp105 expression was high (score 2 or 3) in 31 cases and low (score 0 or 1) in 53 cases; however, it was not significantly correlated with age, nuclear grade, pathological tumor stage and previous intravesical Bacillus Calmette-Guérin immunotherapy. Female gender, lymphovascular invasion and lymph node metastasis were associated with low Hsp105 scores, although the differences were not statistically significant (P=0.071, 0.061 and 0.175, respectively). However, a high Hsp105 score was significantly associated with a favorable prognosis (P=0.017) and was identified as an independent prognostic factor by multivariate analysis (P=0.032; hazard ratio, 2.34). These findings suggested that the expression of Hsp105 may be a novel indicator of a favorable prognosis in bladder cancer. IntroductionUrinary bladder cancer is the second most common urological cancer and is responsible for 2.0% of cancer-related mortality cases worldwide (1). Muscle invasion is a key factor for the prognosis of patients with bladder cancer. Non-muscle invasive bladder cancer (stages Ta, T1 and Tis) generally has a good prognosis, whereas muscle-invasive bladder cancer (MIBC; stages T2, T3 and T4) frequently develops metastases and has a poor prognosis, with a 5-year survival of 65-70% following radical cystectomy (2,3). However, clinical and pathological markers for the prediction of prognosis of patients with bladder cancer following radical cystectomy have not yet been established.Heat shock proteins (HSPs) are stress proteins released in response to various stress factors, such as heat, infection, ischemia and cancer (4). The expression of HSPs in cancer cells has been implicated in the regulation of apoptosis (5,6). HSPs also modulate cancer cell immunogenicity (7,8). Heat shock protein 105 (Hsp105) is a high-molecular-weight protein that belongs to the Hsp105̸110 family. It is one of several cancer̸testis antigens that were identified by serological analysis of antigens by recombinant expression cloning (SEREX) (9). Previous studies have suggested that Hsp105 enhances stress-induced apoptosis in embryonal cells (10), while suppressing stress-induced apoptosis in neuronal (11) and cancer cells (12,13). Hosaka et al (12) reported that the knockdown of Hsp105 induced apoptosis in the HCT116 human colon cancer and the KATO-3 human gastric cancer cell lines. Furthermore, Hsp105 was shown to be ove...

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Section: Discussionmentioning

confidence: 99%

High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy

Kawai

Enomoto

Morikawa

et al. 2013

Molecular and Clinical Oncology

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“…Hsp60 is a chaperonin localized to the inner mitochondrial membrane and C. Campanella et al matrix and, less frequently, to extramitochondrial sites (Soltys and Gupta, 1996, 1997Cappello et al, 2008). Hsp60 is constitutively expressed under normal conditions, but its levels can increase (as determined by immunohistochemical methods for example) in pre-neoplastic lesions (Cappello et al, 2002(Cappello et al, , 2003a(Cappello et al, , 2003bFan et al, 2006) and in many advanced cancers (Schneider et al, 1999;Cappello et al, 2005;Urushibara et al, 2007). The main function of the mitochondrial Hsp60 is considered to be assistance in the folding and degradation of mitochondrial proteins (Garrido et al, 2001;Levy-Rimler et al, 2002;Fersht and Daggett, 2002;Parcellier et al, 2003).The involvement of Hsp60 in the process of apoptosis and tumorigenesis is still under debate.…”

Section: Discussionmentioning

confidence: 99%

Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells

Campanella¹,

Bucchieri²,

Ardizzone³

et al. 2009

Eur J Histochem

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Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cells

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“…Its overexpression has been reported in exocervix, prostate and colorectal carcinogenesis (44). Hsp60 can be induced by photofrin-mediated photodynamic therapy (PDT) in a PDT-induced resistant colon cancer cell line (45) and is a good prognostic marker to ESCC (44) and neoadjuvant chemoradiation in bladder cancer (46).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Identification of 5-fluorouracil response proteins in colorectal carcinoma cell line SW480 by two-dimensional electrophoresis and MALDI-TOF mass spectrometry

Wong

Chan

et al. 2008

Oncol Rep

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Colorectal cancer (CRC) is the second most prevalent cause of cancer-related deaths in the Western world. 5-Fluorouracil (5-FU) is a standard chemotherapeutic drug to treat CRC. However, the response rate is less than 20% and patients who have responded to 5-FU may become resistant. Therefore there is an urgent need to examine the 5-FU response proteins so that patients with no response to 5-FU can change to other treatment strategies promptly. In this study, the proteomic expression profile in a CRC cell line SW480 before and after 5-FU treatment was examined using 2-dimensional electrophoresis technology. Fourteen proteins with differential expression were identified using mass spectrometry and 7 of them were validated using immunocytochemical (ICC) staining. Protein identification indicated that cyclophilin A, cytokeratin 19 (CK19), cytokeratin 8 (CK8), ras-related nuclear protein, heat shock protein 27 (hsp27) and peroxiredoxin 6 (Prx 6) were upregulated whereas heat shock protein 60 (hsp60), cytokeratin 18 (CK18), cytokeratin 9 (CK9), carbamoylphosphate synthetase I, α-enolase, heat shock protein 70 (hsp70), nm23 and ß-actin were down-regulated. Seven of the 14 proteins detected were validated by ICC staining, which showed that the expression of hsp27, Prx 6 and hsp70 correlated with that from proteomics profiling. Our results suggest that hsp27, Prx 6 and hsp70 are potential 5-FU response proteins and they may represent potential targets for further evaluation in other 5-FU-sensitive and-resistant CRC cell lines.

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HSP60 may Predict Good Pathological Response to Neoadjuvant Chemoradiotherapy in Bladder Cancer

Abstract: Positive HSP60 expression prior to CRT may predict good pathological response to low-dose neoadjuvant CRT in invasive or high-risk superficial bladder cancer.

Cited by 28 publications

References 16 publications

High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy

High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy

Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells

Identification of 5-fluorouracil response proteins in colorectal carcinoma cell line SW480 by two-dimensional electrophoresis and MALDI-TOF mass spectrometry

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