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Effect of IL-6 overexpression on the metastatic potential of rat hepatocellular carcinoma cells

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Abstract

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 retroviral 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. Viral 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'st-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 5×106 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.

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Authors and Affiliations

  1. the Department of Pathology, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island, USA

    Edgar A. Sotomayor MD

  2. Department of Surgery, University of Pisa, Italy

    Roberto Spisni MD

  3. Dept. of Surgery, Div. of Surgical Research, Rhode Island Hospital, 593 Eddy Street, 02903, Providence, RI

    Jonathan S. Reichner PhD, James A. Mulligan MS, Jorge E. Albina MD & Kirby I. Bland MD

Authors
  1. Jonathan S. Reichner PhD
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  2. James A. Mulligan MS
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  3. Roberto Spisni MD
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  4. Edgar A. Sotomayor MD
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  5. Jorge E. Albina MD
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  6. Kirby I. Bland MD
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Reichner, J.S., Mulligan, J.A., Spisni, R. et al. Effect of IL-6 overexpression on the metastatic potential of rat hepatocellular carcinoma cells. Annals of Surgical Oncology 5, 279–286 (1998). https://doi.org/10.1007/BF02303786

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  • DOI: https://doi.org/10.1007/BF02303786

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