Tumors secreting human TNF/cachectin induce cachexia in mice.
Anorexia and weight loss are serious complications that adversely effect the prognosis of cancer patients. It has been suggested that TNF/cachectin may cause cachexia. To determine if TNF/cachectin can induce progressive weight loss in tumor-bearing animals, a clone of the human TNF/cachectin gene was isolated and inserted into a mammalian expression vector. This construct was transfected into CHO cells, and a cell line (CHO/TNF-20) that secretes TNF/cachectin was isolated. A cell line (CHO/CMV-Neo) that contains the same expression vector without the TNF/cachectin gene was also isolated. Nude mice injected intraperitoneally with CHO/TNF-20 cells died more quickly than mice injected with CHO/CMV-Neo cells. Eighty-seven percent of mice inoculated intramuscularly with CHO/TNF-20 cells developed severe cachexia and weight loss. All mice bearing CHO/CMV-Neo tumors maintained or increased their body weight. We conclude that mice bearing tumors that secrete TNF/cachectin develop progressive wasting and die more quickly than mice bearing control tumors.
D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000209:etiology*; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts; D006023:Glycoproteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism*; D010053:Ovary; D011994:Recombinant Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha