Progressive growth of human papillomavirus type 16-transformed keratinocytes is associated with an increased release of soluble tumour necrosis factor (TNF) receptor.
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.
Malejczyk
J
J
Department of Histology and Embryology, Warsaw Medical School, Poland.
Malejczyk
M
M
Breitburd
F
F
Majewski
S
S
Schwarz
A
A
Expert-Besançon
N
N
Jablonska
S
S
Orth
G
G
Luger
T A
TA
D002278:Carcinoma in Situ / Q000473:pathology / Q000821:virology; D002455:Cell Division / Q000502:physiology; D002472:Cell Transformation, Viral; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014846:Vulvar Neoplasms / Q000473:pathology / Q000821:virology
D004279:DNA, Viral; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha