Autophagy markers and RNA-dependent protein kinase (PKR) activity in osteosarcoma diagnosis and treatment

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Background: Osteosarcoma is bone malignancy that most commonly affects children and adolescents. A combination of surgery and chemotherapy has reduced the mortality rate in the past decades; however the mortality rate due to osteosarcoma metastasis continues to be very high. Autophagy is a regulatory mechanism that degrades cytoplasmic components in normal and malignant cells and helps maintain cellular homeostasis. To understand the association and mechanism of autophagy in osteosarcoma, we have investigated the expression of autophagy markers in osteosarcoma patients. Methods: Immunohistochemistry and western blot analyses were used to detect and quantitate autophagy markers and proteins in tumor and control tissues. Results: We show that immunohistochemical analysis of tissue samples (59 osteosarcoma and 59 normal control samples) indicates that the levels of various autophagy markers are increased in osteosarcoma patients compared to the normal tissues. Also, western blot analysis of 10 pairs of osteosarcoma and adjacent normal tissues reveals an increased conversion of the autophagy marker protein LC3I to LC3II by several folds in osteosarcoma. Furthermore, RNA-dependent protein kinase (PKR) protein activity is decreased in osteosarcoma patients. Conclusions: Our findings indicate that autophagy is induced during osteosarcoma and the induction of autophagy is associated with PKR activity. We speculate that autophagy markers coupled with PKR could be relevant to the prognosis and targeted treatment of osteosarcoma.

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