Overexpression of thrombospondin-1 in stromal myofibroblasts is associated with tumor growth and nodal metastasis in gastric carcinoma.
OBJECTIVE
The roles of thrombospondin-1 (THBS-1) in tumor growth and metastasis are complicated and its function as a cancer inhibitor or promoter remains controversial. This clinical study investigated the functional roles of THBS-1 in gastric carcinoma by examining the expression patterns of THBS-1 protein and mRNA levels during gastric cancer development.


METHODS
Eighty-two gastric carcinomas were included in this study. THBS-1, α-smooth muscle actin, and CD34 proteins were localized by immunohistochemical staining, and the levels of THBS-1 mRNA were quantified by real-time polymerase chain reaction.


RESULTS
THBS-1 mRNA expression in gastric carcinoma tissues was significantly higher than in adjacent non-cancerous stomach tissues (P = 0.03). Tumor THBS-1 mRNA expression level was significantly related to lymph node metastasis (P = 0.031), tumor size (P = 0.021) and patient age (P = 0.005). THBS-1 protein was mainly located in stromal myofibroblasts, and was undetectable in tumor cells. Myofibroblasts may be mainly derived from stromal fibroblasts in gastric cancer. The abundance of myofibroblasts was positively correlated with tumor growth and nodal metastasis in gastric carcinoma (P = 0.03, P = 0.0008, respectively).


CONCLUSIONS
This clinical study revealed that overexpression of THBS-1 in stromal myofibroblasts is associated with tumor growth and nodal metastasis in gastric carcinoma. THBS-1 may activate latent transforming growth factor-β1 to stimulate fibroblasts to differentiate into myofibroblasts, though further studies are needed to validate this hypothesis. These results suggest that THBS-1 and myofibroblasts may serve as novel targets for strategies aimed at protection against and treatment of gastric carcinoma.
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center of Molecular Medicine, Fujian Medical University, Fuzhou, China.
Xian-Dong
XD
Lin
Shu-Qin
SQ
Chen
Yuan-Lin
YL
Qi
Jin-Wei
JW
Zhu
Yang
Y
Tang
Jian-Yin
JY
Lin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000737:chemistry* / Q000473:pathology; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000737:chemistry; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology*; D019700:Thrombospondin 1 / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019700:Thrombospondin 1