Thumbnail
Access Restriction
Open

Author Koukourakis, Michael I. ♦ Kalamida, Dimitra ♦ Mitrakas, Achilleas ♦ Pouliliou, Stamatia ♦ Kalamida, Sofia ♦ Sivridis, Efthimios ♦ Giatromanolaki, Alexandra
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANIMAL TISSUES ♦ BIOPSY ♦ BUILDUP ♦ CARCINOMAS ♦ DETECTION ♦ IN VITRO ♦ IN VIVO ♦ IRRADIATION ♦ MICROSCOPY ♦ PATIENTS ♦ PHENOTYPE ♦ PROSTATE ♦ RADICALS ♦ RADIOSENSITIVITY ♦ RADIOTHERAPY
Abstract Introduction: Radiotherapy is an equivalent alternative or complement to radical prostatectomy, with high therapeutic efficacy. High risk patients, however, experience high relapse rates, so that research on radio-sensitization is the most evident route to improve curability of this common disease. Materials and methods: In the current study we investigated the autophagic activity in a series of patients with localized prostate tumors treated with radical radiotherapy, using the LC3A and the LAMP2a proteins as markers of autophagosome and lysosome cellular content, respectively. The role of autophagy on prostate cancer cell line resistance to radiation was also examined. Results: Using confocal microscopy on tissue biopsies, we showed that prostate cancer cells have, overall, high levels of LC3A and low levels of LAMP2a compared to normal prostate glands. Tumors with a ‘highLC3A/lowLAMP2a’ phenotype, suggestive of intensified lysosomal consumption, had a significantly poorer biochemical relapse free survival. The PC3 radioresistant cell line sustained remarkably its autophagic flux ability after radiation, while the DU145 radiosensitive one experiences a prolonged blockage of the autophagic process. This was assessed with aggresome accumulation detection and LC3A/LAMP2a double immunofluorescence, as well as with sequestrosome/p62 protein detection. By silencing the LC3A or LAMP2a expression, both cell lines became more sensitive to escalated doses of radiation. Conclusions: High base line autophagy activity and cell ability to sustain functional autophagy define resistance of prostate cancer cells to radiotherapy. This can be reversed by blocking up-regulated components of the autophagy pathway, which may prove of importance in the field of clinical radiotherapy. - Highlights: • High LC3A and low LAMP2a levels is a frequent expression pattern of prostate carcinoma. • This pattern of intensified autophagic flux relates with high relapse rates after radiotherapy. • The PC3 radio-resistant cell line sustains remarkably its autophagic flux ability after radiation. • Irradiation of the DU145 radio-sensitive cell line blocks the autophagic flux. • Intense autophagy activity defines prostate cancer radio-resistance, in vivo and in vitro.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-05-29
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 461
Issue Number 2


Open content in new tab

   Open content in new tab