Heat shock protein 70 (HSP70) after laser thermotherapy of an adenocarcinoma transplanted into rat liver.
The heat shock proteins (HSPs) HSP70 and gp96 from necrotic tumour cells are considered to function as chaperones in presenting tumour antigens. We therefore studied HSP70 and immune cells in a transplantable carcinoma in the liver of rats after interstitial laser thermotherapy (ILT). Experiments were performed in Wistar FU rats using a dimethyl-hydrazine-induced adenocarcinoma implanted into the left lateral lobe of the liver. Rats were randomized to one of the following groups: a) ILT of tumour, b) sham ILT, or c) control. ILT was suboptimal and was performed at a steady-state temperature of 43 degrees C at the tumour margin for 30 minutes. Rats were killed 15 minutes, 5 hours, 10 hours, 15 hours or 12 days after treatment. Double immunohistochemistry was performed for HSP70 and ED1 macrophages or CD8 lymphocytes, and ELISA for serum concentrations of HSP70. After ILT, there was an increase of HSP70 immunoreactivity in tumours as compared to sham ILT. At the same time, tumour cells affected by ILT showed a shift of HSP70 from the cytoplasm to the nucleus with a peak at 10 hours. Few CD8-positive cells were found. There was an increase of tumour-infiltrating ED1 macrophages after ILT as compared to sham ILT at 10-15 hours after treatment. HSP70 was present in ED1 macrophages significantly more frequently after ILT than after sham ILT, and this was true both for HSP70 localized to the surface and the cytoplasm of the macrophage. There was a significant increase in serum HSP70 during the first 15 hours after ILT. In conclusion, laser thermotherapy resulted in increased HSP70 immunoreactivity within tumours and HSP70 shifts from cytoplasm to nucleus. Furthermore, it resulted in increased numbers of tumour-infiltrating macrophages and an increased presence of HSP70 in the membrane and cytoplasm of these macrophages.
Ivarsson
Kjell
K
Department of Surgery, Lund University, SE-221 85 Lund, Sweden.
Myllymäki
Linda
L
Jansner
Karin
K
Bruun
Anitha
A
Stenram
Unne
U
Tranberg
Karl-Göran
KG
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003593:Cytoplasm / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006979:Hyperthermia, Induced; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D018840:HSP70 Heat-Shock Proteins