Clinical significance of secreted protein acidic and rich in cystein in esophageal carcinoma and its relation to carcinoma progression.
BACKGROUND
Secreted protein acidic and rich in cystein (SPARC) is a small extramatrix-associated protein. Its production increases during angiogenesis and enhances matrix metalloproteinase-2 (MMP-2) expression. The goal of this study was to show the clinical relevance of SPARC and its relation to MMP-2 expression in esophageal carcinoma patients.


METHODS
The authors investigated SPARC mRNA expression in 48 tissue samples of esophageal tumors characterized by MMP-2 mRNA expression in a Northern blot analysis. Western blot analysis and immunohistochemistry were also performed in esophageal carcinoma tissue samples.


RESULTS
All 48 tissue specimens had high expression of SPARC mRNA. Quantitative evaluation showed that high SPARC mRNA was associated significantly with lymph node metastasis (P = 0.05) and poorer prognosis (P = 0.025). Expression of SPARC mRNA was associated significantly with MMP-2 mRNA expression (R = 0.65; P < 0.01). Both SPARC and MMP-2 were immunolocalized intensely in carcinoma and stromal cells, whereas normal esophageal mucosa and submucosa did not express SPARC. The 35-kilodalton cleaved SPARC was detected in esophageal carcinoma tissue specimens by Western blot analysis and it was associated with MMP-2 mRNA expression.


CONCLUSIONS
In terms of clinical significance, SPARC accumulation may reflect a functional correlation with MMP-2 and the associated expression could play a key role in the progression of esophageal carcinoma.
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Keishi
K
Yamashita
Sunil
S
Upadhay
Kohshi
K
Mimori
Hiroshi
H
Inoue
Masaki
M
Mori
D015152:Blotting, Northern; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality* / Q000556:secondary; D016022:Case-Control Studies; D017931:DNA Primers; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis
D017931:DNA Primers; D015676:Osteonectin; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2