Heat shock protein 70-2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth.

Nirmala Jagadish,Rajive Kumar,Anju Gupta,Nirmal Kumar Lohiya,Trilok Chand Sadasukhi,Abdul S Ansari,Sumit Agarwal,Deepak Parashar,Vitusha Suri,Vaishali Suri,Anil Suri,Namita Gupta

doi:10.1186/s12885-016-2592-7

Abstract

BackgroundColorectal cancer (CRC) is the third leading cause of cancer related deaths worldwide both in men and women. Our recent studies have indicated an association of heat shock protein 70–2 (HSP70-2) with bladder urothelial carcinoma. In the present study, we investigated the association of HSP70-2 with various malignant properties of colorectal cancer cells and clinic-pathological features of CRC in clinical specimens.MethodsHSP70-2 mRNA and protein was investigated expression by RT-PCR, immunohistochemistry, immunofluorescence, flow cytometry and Western blotting in CRC clinical specimens and COLO205 and HCT116 cell lines. Plasmid-based gene silencing approach was employed to study the association of HSP70-2 with various malignant properties of COLO205 and HCT116 cells in in vitro and with tumor progression in in vivo COLO205 human xenograft mice model.ResultsHSP70-2 expression was detected in 78 % of CRC patients irrespective of various stages and grades by RT-PCR and IHC. Our analysis further revealed that HSP70-2 expression was detected in both COLO205 and HCT116 cell lines. Ablation of HSP70-2 expression resulted in reduced cellular growth, colony forming ability, migratory and invasive ability of CRC cells. In addition, ablation of HSP70-2 expression showed significant reduction in tumor growth in COLO205 human xenograft in in vivo mouse model.ConclusionCollectively, our results indicate that HSP70-2 is associated with CRC clinical specimens. In addition, down regulation of HSP70-2 expression reduces cellular proliferation and tumor growth indicating that HSP70-2 may be a potential therapeutic target for CRC treatment.

Highlights

Colorectal cancer (CRC) is the third leading cause of cancer related deaths worldwide both in men and women
We demonstrated the involvement of heat shock protein 70–2 (HSP70-2) in various malignant properties of CRC cell line models by employing plasmid driven short hairpin RNA interference approach
HSP70-2 gene is expressed in CRC cells and specimens The HSPA2 gene expression was examined by RT-PCR in CRC tissue specimens and CRC cells (COLO205 and HCT116)

Summary

Introduction

Colorectal cancer (CRC) is the third leading cause of cancer related deaths worldwide both in men and women. Our recent studies have indicated an association of heat shock protein 70–2 (HSP70-2) with bladder urothelial carcinoma. We investigated the association of HSP70-2 with various malignant properties of colorectal cancer cells and clinic-pathological features of CRC in clinical specimens. Colorectal cancer (CRC) is the third leading cause of cancer related deaths in women and second in men in developed countries [1]. When diagnosed at later stages (stage III & IV), there are Recently, a member of heat shock protein (HSP) protein family, HSP70-2 has been documented to be associated with bladder carcinoma [4], cervical carcinoma [5], esophageal carcinoma [6] and renal cell carcinoma [7].

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