HSP60 Predicts Survival in Advanced Serous Ovarian Cancer

ObjectiveHeat shock protein 60 (HSP60) plays an essential role in malignant cell survival. We evaluated the prognostic and treatment predictive value of HSP60 in advanced ovarian cancer.MethodsFresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 fulfilled the eligibility criteria, that is, International Federation of Gynecology and Obstetrics stage IIC-IV, serous/endometrioid tumors, platinum-based chemotherapy, and specimens with 50% tumor cells or greater. Heat shock protein 60 mRNA and protein expression was determined by real-time polymerase chain reaction and immunohistochemistry. We estimated the association between HSP60 and overall survival (OS) and platinum-free interval (PFI) by Cox proportional hazards models and its relationship with treatment response by Fisher’s exact test. Median follow-up was 60 months.ResultsHigh HSP60 mRNA expression was associated with shorter OS (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.3–8.5) and PFI (HR, 3.3; 95% CI, 1.5–7.2). Likewise, high HSP60 protein expression was associated with shorter OS (HR, 3.2; 95% CI, 1.5–7.1) and PFI (HR, 2.6; 95% CI, 1.3–5.3). Median survival for patients with high HSP60 protein expression was 31 months compared with 55 months for low expression cases (P = 0.016). The impact on OS and PFI was even stronger in the subgroup of grade 3 serous tumors. All patients with low HSP60 levels responded to first-line chemotherapy.ConclusionHeat shock protein 60 may identify groups of advanced serous ovarian cancer with different prognosis and treatment response.

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Heat shock protein 60 (HSP60) serves as a potential target for the sensitization of chemoresistant ovarian cancer cells

Gynecologic Oncology ◽

10.1016/j.ygyno.2018.04.165 ◽

2018 ◽

Vol 149 ◽

pp. 72-73 ◽

Cited By ~ 2

Author(s):

N.M. Fletcher ◽

I. Memaj ◽

M.P. Diamond ◽

R.T. Morris ◽

G.M. Saed

Keyword(s):

Ovarian Cancer ◽

Heat Shock ◽

Heat Shock Protein ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Heat Shock Protein 60 ◽

Potential Target ◽

Chemoresistant Ovarian Cancer

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Gene and Protein Expression Profiling of Human Ovarian Cancer Cells Treated with the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin

Cancer Research ◽

10.1158/0008-5472.can-06-2968 ◽

2007 ◽

Vol 67 (7) ◽

pp. 3239-3253 ◽

Cited By ~ 105

Author(s):

Alison Maloney ◽

Paul A. Clarke ◽

Soren Naaby-Hansen ◽

Rob Stein ◽

Jens-Oliver Koopman ◽

...

Keyword(s):

Ovarian Cancer ◽

Heat Shock ◽

Heat Shock Protein ◽

Protein Expression ◽

Cancer Cells ◽

Expression Profiling ◽

Heat Shock Protein 90 ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Gene And Protein Expression

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Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27’s Phosphorylation Status, and Is Mediated by Exosome Liberation

Disease Markers ◽

10.1155/2017/1575374 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

Matthias B. Stope ◽

Gerd Klinkmann ◽

Karoline Diesing ◽

Dominique Koensgen ◽

Martin Burchardt ◽

...

Keyword(s):

Ovarian Cancer ◽

Endoplasmic Reticulum ◽

Heat Shock ◽

Heat Shock Protein ◽

Secretory Pathway ◽

Cell Model ◽

Ovarian Cancer Cells ◽

Hsp27 Phosphorylation ◽

Potential Biomarker ◽

The Impact

The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock. Intra- and extracellular HSP27 amounts were assessed by Western blotting and ELISA. Protein secretion was blocked by brefeldin A and the impact of the HSP27 phosphorylation status was analyzed overexpressing HSP27 phosphomutants. The present study demonstrated that HSP27 secretion by OVCAR-3 and SK-OV-3 cells depends on intracellular HSP27 concentrations. Moreover, HSP27 secretion is independent of the endoplasmic reticulum secretory pathway and HSP27 phosphorylation. Notably, analysis of OC cell-born exosomes not only confirmed the concentration-dependent correlation of HSP27 expression and secretion but also demonstrated a concentration-dependent incorporation of HSP27 protein into exosomes. Thus, secreted HSP27 may become more important as an extracellular factor which controls the tumor microenvironment and might be a noninvasive biomarker.

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Interaction of age and temperature on heat shock protein expression, sperm count, and sperm viability of the adult black soldier fly (Diptera: Stratiomyidae)

Journal of Insects as Food and Feed ◽

10.3920/jiff2020.0017 ◽

2020 ◽

pp. 1-14

Author(s):

A.S. Malawey ◽

H. Zhang ◽

A.S. McGuane ◽

E.M. Walsh ◽

T.W. Rusch ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Protein Expression ◽

Sperm Count ◽

Sperm Viability ◽

Black Soldier Fly ◽

Heat Shock Protein Expression ◽

Temperature Preferences ◽

Males And Females ◽

The Impact

Information regarding black soldier fly (Diptera: Stratiomyidae) adult biology is vital as this is the life stage that produces eggs and thus drives population size. The goal of this study was to determine key biological characteristics of adult black soldier flies as they age in relation to: (1) the thermal preferences (Tsel) of males and females; (2) the impact of temperature on heat shock protein expression in males and females; as well as (3) the sperm count; and (4) the sperm viability in males. Aging significantly impacted male and female temperature preferences. Young males (<24-h-old) preferred warmer temperatures (median=24.3 °C, range=19.3-28.2 °C) compared to females of the same age (median=20.2 °C, range=15.4-26.2 °C). However, in older adults (i.e. 72-h-old males and 48-h-old females), temperature preferences converged between 21 and 24 °C. Temperatures tested did not impact hsp expression in males or females. However, aging males, but not females, had increased expression of the heat shock proteins (hsp) hsp70 and hsp90. Furthermore, age impacted sperm count but not sperm viability in males. In particular, 48-h-old males had the greatest sperm count (322.5/sample) and sperm viability (60-78%) compared to all other aged males. Thermal data in conjunction with sperm data potentially explain why early thermal segregation behaviour between males and females occurs. Once adult males and females reached 72-h-old and 48-h-old, respectively, they exhibited a common thermal preference, which coincided with the greatest number of viable sperm in males. Forcing adults into environments (i.e. cages) outside these selected preferences could result in premature or delayed mating or low fertilisation rates. Future research exploring cage design and conditions are needed to optimise black soldier fly colony maintenance and fertile egg production, and can leverage information such as the results described here.

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