Heat shock protein 70 is acute phase reactant: response elicited by tumor treatment with photodynamic therapy

Abstract

Oxidative stress in photodynamic therapy (PDT)-treated tumor cells is known to instigate a strong upregulation of the expression of heat shock proteins. However, the treatment of mouse Lewis lung carcinoma (LLC) cells with Photofrin™ PDT resulted in the upregulation of heat shock protein 70 (Hsp70) gene not only in these cells but also in co-incubated untreated Hepa 1-6 cells. To investigate whether this phenomenon extends in vivo, LLC tumors growing in C57BL/6 mice were treated with Photofrin™ PDT. The tumors and the livers from the mice were collected at 4, 8, or 24 h after therapy for quantitative reverse transcriptase polymerase chain reaction-based analysis of Hsp70 gene expression. Increased Hsp70 gene expression was detected in both the tumor and liver tissues and was most pronounced at 4 h after PDT. This effect was inhibited by treatment of host mice with glucocorticoid synthesis inhibitor metyrapone. Hsp70 protein levels in the livers of mice bearing PDT-treated tumors gradually decreased after therapy while serum levels increased at 4 h after therapy and then continually decreased. The exposure of in vitro PDT-treated LLC cells to Hsp70 and subsequent flow cytometry analysis revealed binding of this protein to cells that was dependent on PDT dose and more pronounced with dying than viable cells. Thus, following the induction of tumor injury by PDT, Hsp70 can be produced in the liver and spleen as acute phase reactant and released into circulation, from where it can be rapidly sequestered to damaged tumor tissue to facilitate the disposal of dying cells.

PDT‐induced HSP70 externalization up‐regulates NO production via TLR2 signal pathway in macrophages

“…2). Since cytoplasmic HSP70 could translocate onto the cell surface after PDT treatment [25,26], neutralization of HSP70 blocked AC‐induced expression of NO production in macrophages. These results suggest that the translocated HSP70 from AC, which is responsible for the upregulation of iNOS expression in macrophages.…”

The detection and role of heat shock protein 70 in various nondisease conditions and disease conditions: a literature review

“…immune responses and may play a major role in maintaining immune homeostasis (Wachstein et al 2012). In addition, HSP70 has been suggested to exert its cytoprotective action by protecting mitochondria and by interfering with stressinduced apoptotic programming (Merchant and Korbelik 2011). Quantitative studies have confirmed numerous detection methods for HSP70, and HSP70 has been associated with various nondisease and disease conditions, demonstrating its clinical significance.…”

“…HSP70 is also a member of the molecular chaperone family, which is involved in protecting cells against various types of stress. In addition, HSP70 has a protective role in tissue injury: it is produced in the liver and spleen as an acute-phase reactant and is released into the circulation to facilitate the disposal of dying cells (Merchant and Korbelik 2011). HSPs have been reported to play important roles in the activation and maturation of DCs (Tsan and Gao 2009).…”

Hormonal component of tumor photodynamic therapy response

“…In our studies on the role of HSP70 in tumor PDT response, we discovered that HSP70 gene becomes upregulated in the liver and spleen of mice bearing PDT-treated tumors 22 . Our hypothesis that glucocorticoid hormones are responsible for this effect is now supported by two findings.…”