Interleukin-6 enhances motility of breast carcinoma cells

  • Pravinkumar B. Sehgal
  • Igor Tamm
Part of the Experientia Supplementum book series (EXS, volume 59)


Interleukin-6 (IL-6) is the major systemic mediator of the early host response to infection and injury (the “acute phase response”). Furthermore, IL-6 is often detected in the peripheral circulation and in the local neoplastic tissue in cancer patients. IL-6 has distinctive effects on epithelial cells depending upon the cell type examined. IL-6 enhances proliferation of normal human keratinocytes without affecting cell morphology. In contrast, IL-6 inhibits the proliferation of ductal breast carcinoma cell lines T-47D, ZR-71-1 and MCF-7. In addition to, but independent of, the inhibition of cell proliferation, IL-6 induces a cellular phenotype in the typically epitheliod T-47D and ZR-75-1 cells, which is characterized by fibroblastoid morphology, increased cell-cell separation even within preformed colonies, decreased adherens type junction formation (desmosomes and focal adhesions), and enhanced motility. Time-lapse cinemicrography of T-47D and wild-type ZR-75-1 cells reveals increased local movement of IL-6-treated cells and also movement of these cells over considerable distances. The effects of IL-6 on breast cancer cell proliferation and motility are reversible by removal of IL-6 from the culture medium. Time-lapse cinemicrography reveals that in clone B ZR-75-1 cells, which are not sensitive to the DNA synthesis-inhibitory effect of IL-6 or to its cell-separating effect on preformed colonies, IL-6 can still block rapid readherence of post-mitotic cells to their neighbors and to the substratum leading to enhanced dispersal of cancer cells into the culture medium. In wild-type ZR-75-1 cells, 12-O-tetradecanoyl phorbol ester (TPA) exerts a cell-scattering effect on breast cancer cells without inhibiting cell proliferation. Combined treatment with IL-6 and TPA produces a cell-scattering effect that greatly exceeds in magnitude and speed the phenotypic change elicited by either reagent alone. Staurosporine blocks cell-scattering caused by TPA but not that caused by IL-6 suggesting that IL-6 and TPA elicit similar phenotypic changes in breast cancer cells via different pathways. Taken together, these findings identify a previously unrecognized property of IL-6, that of enhancing cell motility.


Normal Human Keratinocytes Final Magnification Enhance Cell Motility Compact Coloni Phase Contrast Objective 
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Copyright information

© Birkhäuser Verlag Basel/Switzerland 1991

Authors and Affiliations

  • Pravinkumar B. Sehgal
    • 1
  • Igor Tamm
    • 1
  1. 1.The Rockefeller UniversityNew YorkUSA

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