Cancer Res Treat.  2008 Sep;40(3):127-132.

The Bone Morphogenesis Protein-2 (BMP-2) is Associated with Progression to Metastatic Disease in Gastric Cancer

• Park Y
• Kim JW
• Kim DS
• Kim EB
• Park SJ
• Park JY
• Choi WS
• Song JG
• Seo HY
• Oh SC
• Kim BS
• Park JJ
• Kim YH
• Kim JS

Abstract

PURPOSE
Bone Morphogenetic Proteins (BMPs) are members of the TGF-beta superfamily and it has been demonstrated that BMPs enhance migration, invasion and metastasis. The purpose of this study was to identify the association between the serum BMP-2 level and the progression status of gastric cancer.
MATERIALS AND METHODS
Fifty-five patients with metastatic gastric cancer (metastatic disease group), six patients with early gastric cancer without lymph node metastasis (the EGC group), and ten healthy control subjects were enrolled in this study. The serum BMP-2 level was quantified by use of a commercially available ELISA kit. In EGC group patients and patients with metastatic disease, whole blood was obtained before endoscopic mucosal resection and before the commencement of a scheduled cycle of systemic chemotherapy, respectively.
RESULTS
No significant difference in the mean serum BMP-2 levels was observed between the control subjects and the EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p=1.0). However, the metastatic disease group patients had a significantly higher level of serum BMP (179.61 pg/ml) than the control subjects and EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p<0.0001). Moreover, the mean serum BMP-2 level from patients with a bone metastasis was significantly higher than the mean serum BMP-2 level from patients without a bone metastasis (204.73 pg/ml versus 173.33 pg/ml, p=0.021).
CONCLUSIONS
BMP-2 seems to have a role in progression to metastatic disease in gastric cancer, especially in the late stage of tumorigenesis, including invasion and metastasis. BMP-2 may facilitate bone metastasis in gastric cancer. To confirm these findings, further studies are required with tissue specimens and the use of a cancer cell line.

Keyword

Bone morphogenesis protein-2; BMP-2; Stomach neoplasms; Invasion; Neoplasm metastasis

MeSH Terms

Bone Morphogenetic Proteins
Cell Line
Cell Transformation, Neoplastic
Enzyme-Linked Immunosorbent Assay
Humans
Lymph Nodes
Morphogenesis
Neoplasm Metastasis
Stomach Neoplasms
Transforming Growth Factor beta
Bone Morphogenetic Proteins
Transforming Growth Factor beta

Figure

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  Fig. 1 Serum BMP-2 level in EGC patients and metastatic disease group patients as compared with control subjects. The upper and lower limits of each box represent the interquantile range (25th~75th percentile) and the horizontal line within each box shows the median value. The BMP-2 level was significantly increased in all patients with metastatic disease according to the use of the Wilcoxon rank sum test (p<0.0001). The BMP-2 level in the metastatic disease group shows a statistically significant difference as compared with the control subjects and EGC patients according to the use of the Mann-Whitney U test (p<0.0001, respectively).

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  Fig. 2 Comparison of the serum BMP-2 level in patients without a bone metastasis and patients with a bone metastasis. The upper and lower limits of each box represent the interquantile range (25th~75th percentile), and the horizontal line within each box shows the median value. The mean serum BMP-2 level from patients with a bone metastasis was significantly higher than the mean serum BMP-2 level from patients without a bone metastasis according to the use of the Mann-Whitney U test.

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  Fig. 3 A comparison of the serum BMP-2 level according to the tumor histology. The upper and lower limits of each box represent the interquantile range (25th~75th percentile), and the horizontal line within each box shows the median value. The mean level of serum BMP-2 among each group showed neither a difference nor tendency with differentiation according to the use of the Kruskal-Wallis test.

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