1996 Fiscal Year Final Research Report Summary
Analysis of hematogenous metastasis of human gastric cancer using LacZ gene-tagged tumor cells.
| Project/Area Number |
07670268
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
NAKANISHI Hayao Aichi Cancer Center Research Institute, Laboratory, of Pathology, Section head, 病理学第一部, 室長 (20207830)
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| Co-Investigator(Kenkyū-buntansha) |
OGURI Kayoko National Nagoya Hospital, Clinical Research Institute, Senior Researcher, 臨床研究部, 研究員 (10158826)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Gastric Cancer / Human / LacZ gene / Metastasis / Circulating tumor cells / Lewis carcinoma / Syndecan |
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| Research Abstract |
1. We previously developed a transplantable human gastric carcinoma line with high spontaneous lung metastatic potential in nude mice (GLM-1). We further established a new metastatic, human gastric carcinoma line (GLM-2) and a rat prostatic carcinoma cell line transfected with LacZ gene (PLS30LZ). These cell lines circulate in the bloodstream in cell clusters and form micrometastatic foci in the lung after intravascular growth like GLM-1 cells, as demonstrated by X-Gal and BrdU double staining. This is sharp contrast to the present leucocyte migration model in which tumor cells reaching metastatic site first transmigrate through the endothelium and grow in the extravascular space to form metastatic foci. These results suggest that the metastatic process is diverse and there is a molecular mechanism distinct from the leucocyte model in which sLex, sLea-E selectin and integrin-ECM interactions play a major role in the development of metastasis.
2. Using LacZ gene transfected cells, we fou
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nd that mouse Lewis lung carcinoma cells metastasize to the lung in a similar manner to the leucocyte model. Experimental lung metastasis produced by i.v.injection of the tumor cells, however, was inhibited by heparin but not by RGDS peptide derived from fibronectin. Immunohistochemistry using antisyndecan-2 antibody showed the cell surface expression of this proteoglycan in the tumor cells. These results suggest that a non-integrin cell surface receptor for ECM is involved in the arrest and subsequent micrometastasis formation in this model.
3. Establishment of cultured cell line from GLM-1 transplantable line in a nude mouse not feasifle to data. Primary cultured cells cease growth after 5-10 generations in culture. Expression of LacZ gene in the above transfected non-metastatic human gastric carcinoma cell line (HSC-39) is relatively weak and unstable. Immortalization of GLM-1 tumor with SV40 T antigen and LacZ gene transfection using electroporation technique are now on going. Further in vivo studies are needed to clarify the molecular basis of the natural history of human gastric cancer metastasis. Less
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