Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS:
cDNA microarray revealed that high osteopontin mRNA expression was associated with poor survival of ESCC patients (P = 0.029). In immunohistochemistry, osteopontin protein expression was associated with poor prognosis (P < 0.001), distant lymph node metastasis (P = 0.0004), tumor staging (P = 0.027), and histologic grade (P = 0.024). Multivariate analysis showed that osteopontin overexpression was the strongest independent prognostic factor among nine clinicopathologic variables (P < 0.001). Among cell lines tested, 30 had overexpressed osteopontin protein compared with a normal esophageal epithelial cell line. An inducible shRNA vector against osteopontin successfully down-regulated osteopontin expression by 71% to 88% and repressed cell motility by 69% to 97%, cell invasion by 59% to 71%, tumor formation by 56% to 92%, and lymph node metastasis by 50% to 67% in HSA/c cells. CONCLUSIONS: Our findings suggest that osteopontin overexpression may play an important role in progression of ESCC and osteopontin could be a potential target of ESCC therapy.
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Authors | Tetsuo Ito, Yosuke Hashimoto, Eiji Tanaka, Takatsugu Kan, Shigeru Tsunoda, Fumiaki Sato, Motoshige Higashiyama, Tomoyuki Okumura, Yutaka Shimada |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 12
Issue 4
Pg. 1308-16
(Feb 15 2006)
ISSN: 1078-0432 [Print] United States |
PMID | 16489088
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Messenger
- RNA, Small Interfering
- SPP1 protein, human
- Sialoglycoproteins
- Spp1 protein, mouse
- Osteopontin
- Doxycycline
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Topics |
- Administration, Oral
- Adult
- Aged
- Aged, 80 and over
- Animals
- Base Sequence
- Carcinoma, Squamous Cell
(drug therapy, genetics, pathology)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Doxycycline
(administration & dosage, pharmacology, therapeutic use)
- Esophageal Neoplasms
(drug therapy, genetics, pathology)
- Female
- Gene Expression Regulation, Neoplastic
- Genetic Vectors
(genetics)
- Humans
- Lymphatic Metastasis
(genetics, prevention & control)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Middle Aged
- Molecular Sequence Data
- Neoplasms, Experimental
(drug therapy, genetics, pathology)
- Oligonucleotide Array Sequence Analysis
- Osteopontin
- RNA, Messenger
(genetics, metabolism)
- RNA, Small Interfering
(genetics)
- Sialoglycoproteins
(genetics, physiology)
- Transfection
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