Progressive growth of human papillomavirus type 16-transformed keratinocytes is associated with an increased release of soluble tumour necrosis factor (TNF) receptor

Br J Cancer. 1996 Jul;74(2):234-9. doi: 10.1038/bjc.1996.343.


Analysis of conditioned media generated by weakly and highly tumorigenic SKv-1 keratinocyte lines harbouring integrated human papillomavirus type 16 (HPV16) DNA sequences revealed a factor inhibiting TNF-alpha and TNF-beta cytotoxic activity. This inhibitory activity was specifically blocked by htr-9 monoclonal antibody (MAb) recognising 55/60 kDa type I TNF receptor suggesting that it is related to a soluble form of this particular receptor (sTNF-RI). The presence of sTNF-RI was confirmed by Western blot analysis of SKv-1 cell-conditioned medium showing a band of 31.5 kDa as well as by the specific enzyme-linked immunobiological assay (ELIBA). Release of sTNF-RI was a result of shedding because Northern blot analysis showed that SKv-1 cells expressed a full-length TNF-RI mRNA, and radioimmunoprecipitation of TNF-RI from [32S]cysteine-labelled cell extracts demonstrated the presence of normal 55 kDa molecule. Evaluation by ELIBA showed that highly tumorigenic SKv-12 cells released significantly more sTNF-RI than their weakly tumorigenic SKv-11 parental cells. Furthermore, human recombinant as well as SKv cell-derived sTNF-RI stimulated proliferation of weakly tumorigenic SKv-11 cells. This suggests that a progressive growth of some neoplastic cells may be, at least partially, a result of an increased spontaneous release of sTNF-RI that enables the cells to escape from local TNF-alpha-mediated growth inhibition.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma in Situ / pathology
  • Carcinoma in Situ / virology
  • Cell Division / physiology
  • Cell Transformation, Viral*
  • DNA, Viral / genetics
  • Female
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Keratinocytes / virology*
  • Papillomaviridae / genetics*
  • Receptors, Tumor Necrosis Factor / physiology*
  • Solubility
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Vulvar Neoplasms / pathology
  • Vulvar Neoplasms / virology


  • DNA, Viral
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha