A reduction in blood insulin levels as a host endocrine response during tumor development.
It has been previously reported that endogenous insulin levels decrease during tumor growth. We have now studied whether this host endocrine response is independent of the way in which the tumor is induced. For this purpose, animals transplanted with tumor cells induced by 3-methylcholanthrene (MCA) or 7,12-dimethylbenz(a) anthracene (DMBA), or with EL-4 lymphoma cells, and animals that develop autochthonous tumors induced by MCA or the murine mammary tumor virus (MMTV) were used. These procedures result in the induction of tumors of different histologic types: fibrosarcoma, mammary adenocarcinoma and lymphoma. The results obtained showed that a reduction in insulin levels preceded the overt appearance of tumors in all models of syngeneic or autochthonous tumors studied but not when DMBA-induced tumor cells were administered into allogeneic recipients. Reduced levels of insulin before tumor detection appeared to affect the onset of MCA-induced tumors. Indeed, those mice with a late tumor onset were those that had a more pronounced decrease in insulin blood levels during the induction phase of autochthonous MCA-induced tumors. Soluble factors associated with tumor growth seem to mediate the reduction in insulin blood levels in mice transplanted with EL-4 tumor cells. The results obtained indicate that the reduction in insulin levels detected is a consequence of the recognition of tumor cells by the host, and seems to be independent of the histologic type of the neoplastic cells that develop. Pharmacological interventions at the levels of mechanisms that control insulin output should clarify the relevance of decreased levels of this hormone for tumor development.
Besedovsky
H O
HO
Division of Immunophysiology, Institute of Physiology, Medical Faculty, Philipps-University, Deutschhausstrasse 2, 35037, Marburg, Germany. besedovsky@mailer.uni-marburg.de
Normann
S
S
Schardt
M
M
del Rey
A
A
D000818:Animals; D004702:Endocrine Glands / Q000502:physiology*; D005260:Female; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D007328:Insulin