| RRC ID |
52050
|
| 著者 |
Zhang M, Osisami M, Dai J, Keller JM, Escara-Wilke J, Mizokami A, Keller ET.
|
| タイトル |
Bone Microenvironment Changes in Latexin Expression Promote Chemoresistance.
|
| ジャーナル |
Mol Cancer Res
|
| Abstract |
Although docetaxel is the standard of care for advanced prostate cancer, most patients develop resistance to docetaxel. Therefore, elucidating the mechanism that underlies resistance to docetaxel is critical to enhance therapeutic intervention. Mining cDNA microarray from the PC-3 prostate cancer cell line and its docetaxel-resistant derivative (PC3-TxR) revealed decreased latexin (LXN) expression in the resistant cells. LXN expression was inversely correlated with taxane resistance in a panel of prostate cancer cell lines. LXN knockdown conferred docetaxel resistance to prostate cancer cells in vitro and in vivo, whereas LXN overexpression reduced docetaxel resistance in several prostate cancer cell lines. A mouse model of prostate cancer demonstrated that prostate cancer cells developed resistance to docetaxel in the bone microenvironment, but not the soft tissue microenvironment. This was associated with decreased LXN expression in prostate cancer cells in the bone microenvironment compared with the soft tissue microenvironment. It was identified that bone stromal cells decreased LXN expression through methylation and induced chemoresistance in prostate cancer in vitro These findings reveal that a subset of prostate cancer develops docetaxel resistance through loss of LXN expression associated with methylation and that the bone microenvironment promotes this drug resistance phenotype.Implications: This study suggests that the LXN pathway should be further explored as a viable target for preventing or reversing taxane resistance in prostate cancer. Mol Cancer Res; 15(4); 457-66. ©2017 AACR.
|
| 巻・号 |
15(4)
|
| ページ |
457-466
|
| 公開日 |
2017-4-1
|
| DOI |
10.1158/1541-7786.MCR-16-0392
|
| PII |
1541-7786.MCR-16-0392
|
| PMID |
28087740
|
| PMC |
PMC5380553
|
| MeSH |
Animals
Bone and Bones / cytology*
Bone and Bones / drug effects
Cell Line, Tumor
DNA Methylation
Docetaxel
Down-Regulation*
Drug Resistance, Neoplasm*
Gene Expression Profiling / methods
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Nerve Tissue Proteins
Oligonucleotide Array Sequence Analysis / methods
Prostatic Neoplasms / drug therapy
Prostatic Neoplasms / genetics*
Stromal Cells
Taxoids / administration & dosage*
Taxoids / pharmacology
Tumor Microenvironment
Tumor Suppressor Proteins / genetics*
Xenograft Model Antitumor Assays
|
| IF |
4.63
|
| 引用数 |
6
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224) |
