HSP70: a promising target for laryngeal carcinoma radiaotherapy by inhibiting cleavage and degradation of nucleolin

HSP70 is the most important member of heat shock protein family, and plays an important role in the cells endogenous protection mechanisms [1,2]. Recent studies have shown that different type of heat shock protein upregulated in different type of tumors, HSPs were associated with histological grade, recurrence and metastasis of malignant tumors [3-6]. However, the role of HSP70 in LSCC is not fully understood.Weber, A et al had reported that HSP70 was significantly upregulated in squamous cell carcinoma of the head and neck (SCCHN) [7]. In our previous studies, we also found that HSP70 highly expressed at 7.7 folds comparing to normal tissue using HG-U133.Plus.2.0 chip (data unpublished). These results suggested that the overexpression of HSP70 was an important biological characteristic of LSCC.Nucleolin(C23) is an abundant nuclear protein located in the dense fibrillar components(DFCs) and granular components(GCs) of nucleoli. It plays essential roles in promoting cell proliferation [8-11]. Our previous studies have shown that HSP70 could interact with C23 and inhibiting H2O2-induced cleavage and degradation of C23, thereby inhibiting reactive oxygen species-induced cell apoptosis [12]. There were two ways for radiotherapy to destruct tumor cells: (1) X-ray directly broke the DNA of the cancer cells into fragmentations, leading to cell apoptosis; (2) X-ray released free radicals from other components (e.g. H2O) in the cells thereby to attack tumor cells. Theoretically, radiotherapy could result in cleavage and degradation of C23 and sequentially kill the tumors.In the present study, we determined whether reduction of HSP70 expression could enhance radiosensitivity of LSCC by increasing C23 cleavage and degradation.High-quality tissue microarray (TMA) was constructed with fifty tumor samples including different stages of LSCC. The clinicopathologic features of the participants included in this analysis were presented in Table 1. Briefly, serial 5-μm sections were cu