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A reduction in blood insulin levels as a host endocrine response during tumor development
H O Besedovsky1, S Normann, M Schardt
1Division of Immunophysiology, Institute of Physiology, Medical Faculty, Philipps-University, Deutschhausstrasse 2, 35037, Marburg, Germany. besedovsky@mailer.uni-marburg.de
Abstract:
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.
Insights
Host endocrine response to cancer involves decreased insulin levels, independent of tumor type. This reduction precedes tumor appearance and may influence tumor onset, suggesting a link between insulin and cancer development.
Area of Science:
- Oncology
- Endocrinology
- Cancer Research
Background:
- Endogenous insulin levels are known to decrease during tumor growth.
- The host's endocrine response during tumor development requires further investigation.
Purpose of the Study:
- To determine if the decrease in host insulin levels during tumor growth is independent of the tumor induction method.
- To investigate the relationship between reduced insulin levels and tumor onset and development.
Main Methods:
- Utilized various tumor models in syngeneic and autochthonous settings, including chemically induced (MCA, DMBA) and virus-induced (MMTV) tumors, as well as lymphoma cells (EL-4).
- Monitored insulin levels before and during tumor development.
- Administered DMBA-induced tumor cells into allogeneic recipients to assess host-tumor interactions.
Main Results:
- A reduction in insulin levels consistently preceded tumor appearance across all studied syngeneic and autochthonous tumor models.
- This reduction was not observed when DMBA-induced tumor cells were transplanted into allogeneic recipients.
- Reduced insulin levels appeared to influence the onset of 3-methylcholanthrene (MCA)-induced tumors, with a more pronounced decrease correlating with a later tumor onset.
- Soluble factors from tumor cells (e.g., EL-4 lymphoma) were implicated in mediating insulin level reduction.
Conclusions:
- The observed decrease in insulin levels is a host response to tumor cells, independent of tumor histology.
- Reduced insulin levels precede tumor detection and may play a role in modulating tumor onset.
- Further research into pharmacological interventions targeting insulin regulation is warranted to understand its relevance in tumor development.