Annals of Surgical Oncology

, Volume 5, Issue 3, pp 279–286

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

  • Jonathan S. Reichner
  • James A. Mulligan
  • Roberto Spisni
  • Edgar A. Sotomayor
  • Jorge E. Albina
  • Kirby I. Bland
Original Articles

DOI: 10.1007/BF02303786

Cite this article as:
Reichner, J.S., Mulligan, J.A., Spisni, R. et al. Annals of Surgical Oncology (1998) 5: 279. doi:10.1007/BF02303786

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.

Key Words

IL-6 Metastasis Hepatocellular carcinoma Rat 

Copyright information

© The Society of Surgical Oncology, Inc. 1998

Authors and Affiliations

  • Jonathan S. Reichner
    • 3
  • James A. Mulligan
    • 3
  • Roberto Spisni
    • 2
  • Edgar A. Sotomayor
    • 1
  • Jorge E. Albina
    • 3
  • Kirby I. Bland
    • 3
  1. 1.the Department of PathologyRhode Island Hospital and Brown University School of MedicineProvidenceUSA
  2. 2.Department of SurgeryUniversity of PisaItaly
  3. 3.Dept. of Surgery, Div. of Surgical ResearchRhode Island HospitalProvidence