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YB-1 suppression induces STAT3 proteolysis and sensitizes renal cancer to interferon-α.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2013 Mar; Vol. 62 (3), pp. 517-27. Date of Electronic Publication: 2012 Sep 30. - Publication Year :
- 2013
-
Abstract
- Renal cell carcinoma (RCC) accounts for 80-95 % of kidney tumors, and approximately 30 % of RCC patients have metastatic disease at diagnosis. Conventional chemotherapy is not effective in patients with metastatic RCC (MRCC); therefore, immunotherapy with interferon-α (IFN-α) has been employed to improve survival. However, the response rate of MRCC to IFN-α therapy is low. We previously reported that a signal transducer and activator 3 (STAT3) polymorphism was a useful diagnostic marker to predict the response to IFN-α therapy in patients with MRCC. Therefore, we hypothesized the inhibition of STAT3 in the addition of IFN-α therapy might be useful. Moreover, the blockage of STAT3 itself has been reported to enhance the antitumor effects. However, because IFN-α is thought to elicit its therapeutic effect via enhancement of an antitumor immune response mediated by lymphocytes that can be activated by IFN-α administrations, it is probable that the suppression of STAT3 in vivo relates to autoimmune disorders. In the present study, we found Y-box binding protein-1 (YB-1) was poorly expressed in T lymphocytes, as compared with cancer tissues. YB-1 was reported to have an important effect on the STAT3 pathway. Suppression of STAT3 by YB-1 inhibition did not seem to enhance the potential risk for autoimmune disorders. Moreover, we found sensitivity to IFN-α was increased by YB-1 suppression, and this suppression did not down-regulate IFN-α activation of T lymphocytes.
- Subjects :
- Animals
Carcinoma, Renal Cell pathology
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Female
Gene Knockdown Techniques
Humans
Interferon-alpha pharmacology
Kidney Neoplasms pathology
Mice
Mice, Inbred BALB C
Mice, Nude
Proteolysis
STAT3 Transcription Factor antagonists & inhibitors
STAT3 Transcription Factor genetics
Transplantation, Heterologous
Tumor Cells, Cultured
Y-Box-Binding Protein 1 pharmacology
Carcinoma, Renal Cell metabolism
Carcinoma, Renal Cell therapy
Interferon-alpha therapeutic use
Kidney Neoplasms metabolism
Kidney Neoplasms therapy
STAT3 Transcription Factor metabolism
Y-Box-Binding Protein 1 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 62
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 23052245
- Full Text :
- https://doi.org/10.1007/s00262-012-1356-8