Effect of IL-6 overexpression on the metastatic potential of rat hepatocellular carcinoma cells
Annals of Surgical Oncology, ISSN: 1068-9265, Vol: 5, Issue: 3, Page: 279-286
1998
- 19Citations
- 8Captures
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Metrics Details
- Citations19
- Citation Indexes19
- 19
- CrossRef13
- Captures8
- Readers8
Article Description
Background: Previous studies demonstrated that excess IL-6 production correlated with the metastatic potential of rat hepatocellular carcinoma cells. In the work reported here a retrovital construct containing the gene for murine IL-6 was introduced into otherwise nonmetastatic tumor cells to directly determine the effect of IL-6 overexpression on tumor metastatic potential. Methods: The clonal cell lines 1682.C.2.9.L0 (L0, poorly metastatic) and 1682.C.2.9.L10 (L10, highly metastatic) were selected from a parental hepatocellular carcinoma induced in ACI rats by feeding an ethionine-containing diet. Vital supernatant was used to infect the PA317 amphotropic cell line, and retrovirus produced from these cells infected the poorly metastatic L0 hepatocellular carcinoma cell line. Neomycin-resistant cells were selected in G418 and designated L0-IL-6. Results: As determined by bioassay, L0 cells produce 10 ± 1.2 U/mL IL-6 in culture, whereas L10 cells release 95 ± 11 U/mL (P < 0.01, Student's t-test). Retroviral-mediated IL-6 gene transfer resulted in the production of 1266 ± 48 U/mL IL-6 by L0-IL-6 cells under identical culture conditions. When an inoculum of 5 x 10 cells is injected subcutaneously, both L0 and L10 cell lines result in primary tumors with equivalent rates of growth; only L10 cells metastasize to the lung, however. A similar inoculation of L0-IL-6 cells produced local tumors in all 24 animals tested. Interestingly, 15 of 24 (62%) animals presented with metastatic nodules in the abdominal cavity, whereas no such tumors were found in animals receiving L10 cells. Conclusion: Overexpression of IL-6 increases metastatic potential of tumor cells, with preferential metastases to the abdominal cavity when compared with tumor cells elaborating endogenous IL-6.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0031811737&origin=inward; http://dx.doi.org/10.1007/bf02303786; http://www.ncbi.nlm.nih.gov/pubmed/9607632; http://link.springer.com/10.1007/BF02303786; http://www.springerlink.com/index/pdf/10.1007/BF02303786; http://www.springerlink.com/index/10.1007/BF02303786; https://dx.doi.org/10.1007/bf02303786; https://link.springer.com/article/10.1007%2FBF02303786
Springer Nature
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