Higher heat shock factor 1 expression in tumor stroma predicts poor prognosis in esophageal squamous cell carcinoma patients.

Yuehua Liao,Lin Zhang,Wanli Liu,Ge Zhang,Ying Xue,Xinwei Feng

doi:10.1186/s12967-015-0703-x

Abstract

BackgroundHeat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in esophageal squamous cell carcinoma (ESCC) remain unknown.MethodsHSF1 was detected in ESCC cell lines, fibroblast cell lines and ESCC xenograft tumors and human ESCC tissues by real-time RT-PCR and western blotting. HSF1 protein expression was analyzed by immunochemistry in 134 ESCC patients followed by correlation with clinicopathological parameters.ResultsHSF1 expression is weak in fibroblast cell 3T3 and moderate in ESCC cell Eca109, but increasing expression of HSF1 was observed in both of 3T3 and Eca109 cells when they interplayed with each other. In Eca109 xenograft tumors, both tumor cells and stromal fibroblasts showed stronger expression of HSF1. In ESCC patients, the HSF1 expression in tumor or in stromal cells was significantly associated with tumor stage, lymph node metastasis and clinical stage. Multivariate analysis demonstrated a significant negative correlation between disease-free survival (DFS), overall survival (OS) and the HSF1 expression in stromal cells (P < 0.05) but not in tumor cells. Additionally, the expression of HSF1 in tumor cells or stromal cells was an independent factor for DFS (P = 0.032 or P = 0.012) and OS (P = 0.017 or P = 0.013) in metastatic ESCC patients but not for locoregional ESCC. ESCC patients with low HSF1 in both tumor cells and stromal cells had the longest survivals (P < 0.001).ConclusionsThe interaction of tumor cells and stromal fibroblasts increases the expression of HSF1 reciprocally in tumor microenvironment. The HSF1 expression in stromal cells was significantly associated with poor prognosis of ESCC.

Highlights

Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis
HSF1 expression in esophageal squamous cell carcinoma (ESCC) and fibroblast cell lines Western blotting and real-time PCR analysis showed that both HSF1 mRNA and protein were expressed differently in three ESCC cell lines: moderately in Eca109 and strongly in Kyse 510 and Kyse 530 (Fig. 1a, b)
Our data reveal that the increasing expression of HSF1 is found in ESCC tumor cells and stromal cells reciprocally when they interplay with each other in the tumor microenvironment

Summary

Introduction

Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. The clinical significance and biologic function of HSF1 in esophageal squamous cell carcinoma (ESCC) remain unknown. Heat shock transcription factor 1 (HSF1) is a major transcriptional regulator of the heat-shock response (HSR) in eukaryotic cells [4]. HSF1 is evoked in response to a variety of cellular stressors by the upregulation of Hsp protein expression. A number of studies have indicated that HSF1 plays a critical role in carcinogenesis, tumor progression and metastasis by regulating the expression of heat shock proteins and other molecular targets [7]. Studies have revealed that HSF1 drives transcription in cancer cells but is capable of reprogramming transcription extensively in cancer-associated fibroblasts (CAFs). The activation of HSF1 in CAFs promotes malignancy in adjacent cancer cells [8]

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