2001 Fiscal Year Final Research Report Summary
Investigation of osteosarocma specific marker for detection of micro-metastasis
| Project/Area Number |
11470304
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
HOTTA Tetsuo NIIGATA UNIVERSITY, Medical Hospital Associate Professor, 医学部・附属病院, 助教授 (00272815)
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| Project Period (FY) |
1999 – 2000
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| Keywords | osteosarocma / micro-metastasis / Cbfa1 / 0sf2 / peripheral blood / PCR-ELISA / ALP |
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| Research Abstract |
Clinically non-osteosarcoma tumors can be observed with osseous matrix, and it is difficult to distinguish such tumors from osteosarcomas only by histological examination. Because the treatment strategy for osteosarcoma is quite different from other malignant neoplasms, it is important to identify a specific marker for osteosarcoma. Some of osteosarcomas reveals elevation of serum alkaline phosphatase (ALP), so ALP was considered one of the tumor marker in osteosarcomas. However, we revealed some of clear cell sarcomas also showed high expression of serum ALP, and we considered ALP has relative low specificity in bone tumors.
Recently, Osf2/Cbfa1 (hereafter called Osf2), a member of the runt family of transcription factors, was identified as an activator forosteoblastic differentiation. In this study, we showed the expression of Osf2 mRNA only in osteosarcoma cell lines while not in non-osteosarcoma cell lines, suggesting that Osf2 mRNA expression is related to the osteoblastic phenotype of osteosarcoma cells. This result suggested that the expression of CBFA1 might be the specific tumor marker for osteosarcoma.
Circulating tumor cells in the blood play a central role in the metastatic process. There have been no reports describing the relationship between lung metastasis and circulating osteosarcoma cells. We developed a system with a polymerase chain reaction assay based on an enzyme-linked immunosorbent assay (PCR-ELISA) to detect circulating osteosarcoma cells in a mouse metastatic model. Osf2 was used as a target gene. One splicing variant of Osf2 mRNA was identified and its expression was restricted to the bones and osteosarcomas. The amount of the splicing variant of Osf2 mRNA was significantly higher in the blood of mice with metastasis than in the blood of the control group. The PCR-ELISA using Osf2 mRNA is a potential method to detect circulating osteosarcoma cells in peripheral blood.
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