Heat shock protein 70 is acute phase reactant: response elicited by tumor treatment with photodynamic therapy.
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.
Merchant
Soroush
S
British Columbia Cancer Agency, B.C. Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC, Canada.
Korbelik
Mladen
M
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000528:radiation effects*; D018840:HSP70 Heat-Shock Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000503:physiopathology / Q000628:therapy; D008175:Lung Neoplasms / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010778:Photochemotherapy; D011485:Protein Binding
D000209:Acute-Phase Proteins; D018840:HSP70 Heat-Shock Proteins