Expressions of HSP70 and HSP27 in Hepatocellular Carcinoma

Abstract

The heat shock proteins (HSPs) are ubiquitous molecules induced in cells exposed to various stress conditions, including carcinogenesis. The HSP70 and HSP27 among HSPs are of special relevance in human cancer inhibiting apoptosis. The aim of this study is to investigate the expressions of HSP70 and HSP27 in hepatocellular carcinoma (HCC) in association to tumor cell proliferation and apoptosis. We examined the expressions of HSP70 and HSP27 by immunohistochemical staining in 71 cases of HCC, and then related their expressions to clinicopathologic parameters and expressions of p53, Ki-67 and Apotag. HSP70 and HSP27 were frequently stained in the cytoplasm and nuclei of tumor cells, but not in the non-neoplastic hepatocytes. Immunoreactivities of HSP70 and HSP27 were observed in 56.3% and 61.9% of HCCs, respectively. HSP70 immunoreactivity correlated with high Ki-67 labeling indices (LIs) (p=0.0159), large tumor size (p=0.0129), presence of portal vein invasion (p=0.0231), and high tumor stage (p=0.0392). HSP27 immunoreactivity significantly related with the subgroup of HBV-associated HCCs (p=0.0003), but not with the others. Both HSP70 and HSP27 immunoreactivities showed no relation to Apotag LIs or p53 immunoreactivity. In conclusion, expressions of HSP70 and HSP27 may play an important role in hepatocarcinogenesis, and especially HSP70 showed a close relationship to the pathological parameters associated with tumor progression and high Ki-67 LIs. Our results could be additional evidence that HSP70 expressions can contribute to not only hepatocarcinogenesis but also tumor progression by promoting tumor cell proliferation.

Suppression of the Inflammatory Cascade is Implicated in Resveratrol Chemoprevention of Experimental Hepatocarcinogenesis

“…Despite fundamental differences among etiological factors for HCC, a universal denominator of the genesis of malignancy happens to be the perpetuation of a woundhealing response triggered by parenchymal cell death as well as the ensuing inflammatory reaction (13). The process of chronic inflammation leads to a stressful condition, and ubiquitous molecules like heat shock proteins (HSPs) are induced in response to stressful stimuli, contributing to hepatocarcinogenesis (14). One of the prominent members of the HSP family is HSP70.…”

Clinical significance of HSP27 expression in colorectal cancer

“…in contrast, its aberrant expression has been reported in a variety of human cancers, including breast (9), ovarian (10), gastric (11), prostate (12), endometrial (13), liver (14), bladder (15) and leukemia (16). Furthermore, elevated HSP27 levels in breast, ovarian, gastric, and prostate cancer is associated with aggressive growth and resistance to chemotherapy or radiotherapy, and hence with a poor prognosis (9)(10)(11)(12).…”

Mechanism of Action of the Anti-cancer Agent, Triptolide

“…This finding is clinically relevant since HSP70 levels in human pancreatic tumor specimens were higher than the adjacent margins (Aghdassi et al 2007). Similar increase in HSP70 expression has also been observed in hepatocellular carcinoma, and this increase in HSP70 levels correlates with poor outcome (Joo et al 2005;Li et al 2007). Consistent with these data, decrease in the levels of HSP70 either by HSP70-targeted siRNA or pharmacological inhibitors like quercetin and triptolide causes cell death in pancreatic cancer cells (Aghdassi et al 2007;Antonoff et al 2009;Dudeja et al 2009;Phillips et al 2007).…”