Regulation of heat shock protein 27 expression of prostatic cells in response to heat treatment.

BACKGROUND

The clinical value of heat-induced coagulation of prostatic tissue is evaluated as a minimally invasive treatment for patients with benign prostatic hyperplasia (BPH) and, more recently, localized prostate cancer (PC). To obtain a more detailed insight on the effect of heat on prostatic cells, heat shock protein (HSP) 27 expression of normal and malignant prostatic cells was studied.

METHODS

In vitro, HSP27 expression of prostatic stromal cells and the human prostate cancer cell line LNCaP was studied by Western blotting when cultured at 37 degrees C. Subsequently, the effect of a sublethal heat shock from 43-49 degrees C for 60 min on HSP27 expression of LNCaP was determined. In vivo, HSP27 expression pattern of nine human prostates, which were treated in vivo by thermoablation with transrectal high-intensity focused ultrasound (HIFU) 3 hr-8 days prior to surgical removal, was analyzed by immunohistochemistry. Untreated BPH (n = 10) and PC (n = 7) specimens served as controls.

RESULTS

Under physiologic conditions (37 degrees C), LNCaP and prostatic stromal cells expressed a 27-kD and 56-kD anti-HSP27 reactive molecule. Following sublethal cell heating, HSP27 (27 kD) expression of LNCaP increased by 3-4-fold in a temperature-dependent manner. In untreated BPH specimens (n = 10), muscle cells stained HSP27-positive in all samples, while epithelial cells (EC) were negative in 6 out of 10 specimens. At the border of the high-intensity focused ultrasound (HIFU) necrosis, increased HSP27 expression was consistently demonstrable (n = 9). HSP27 upregulation was strongest 2-3 hr after HIFU but still demonstrable after 5-8 days. In this border zone, basal and secretory EC as well as muscle cells stained strongly for HSP27.

CONCLUSIONS

Benign and malignant human prostatic cells respond to heat by increased expression of HSP27 in vitro and in vivo. Transrectal HIFU therapy induces intraprostatic thermonecrosis surrounded by a zone characterized by a massive upregulation of HSP27 expression.