Effects of endostatin production on oncogenicity and metastatic activity of HPV16-transformed mouse cells: role of interleukin 1alpha.
Two mouse HPV16-transformed cell lines, viz. MK16 cells, which induce metastasizing tumors, and TC-1 cells, which induce non-metastasizing tumors were transduced with the gene for mouse endostatin. Two clones constitutively expressing endostatin were isolated from each of them. They were denoted ME3 and ME9, and TE2 and TE5, respectively. When inoculated into mice, ME3 cells were non-oncogenic. Nearly all mice inoculated with ME9 cells developed tumors, but considerably later than did the parental MK16 cells and metastasis formation was strongly reduced in these animals. On the other hand, TE2 and TE5 cells displayed oncogenic potential similar to that of the parental cells. To provide more information on these different effects of endostatin production, cell lysates of all six lines studied were tested for the content of 25 factors known to be involved in angiogenesis. The parental MK16 cells differed from the parental TC-1 cells and also from all endostatin producing sublines by a markedly higher production of interleukin 1alpha (IL-1alpha) and, to a lesser extent, by a higher production of several other factors tested. Additional experiments indicated that the suppression of the production of IL-1alpha by the parental MK16 caused by endostatin was due to an autocrine mechanism.
Lakatosova-Andelova
Monika
M
Department of Experimental Virology, Institute of Haematology and Blood Transfusion, Prague 2, Czech Republic.
Duskova
Martina
M
Lucansky
Vincent
V
Paral
Petr
P
Vonka
Vladimir
V
D000818:Animals; D019898:Autocrine Communication; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D017077:Culture Media, Conditioned / Q000378:metabolism; D043169:Endostatins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D011905:Genes, ras; D053582:Interleukin-1alpha / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control / Q000556:secondary / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics*; D013997:Time Factors; D014161:Transduction, Genetic
D017077:Culture Media, Conditioned; C068651:E6 protein, Human papillomavirus type 16; D043169:Endostatins; D053582:Interleukin-1alpha; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16