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Published on: October 30, 2013
Inhibition of methylcholanthrene-induced carcinogenesis by an interferon gamma receptor-dependent foreign body
Zhihai Qin1, Hye-Jung Kim, Jens Hemme
1Institute of Immunology, Free University Berlin, 12200 Berlin, Germany. zhihai@ukbf.fu-berlin.de
Abstract:
The foreign body reaction is one of the oldest host defense mechanisms against tissue damage which involves inflammation, scarring, and encapsulation. The chemical carcinogen methylcholanthrene (MCA) induces fibrosarcoma and tissue damage in parallel at the injection site. Tumor development induced by MCA but not due to p53-deficiency is increased in interferon-gamma receptor (IFN-gammaR)-deficient mice. In the absence of IFN-gammaR, MCA diffusion and DNA damage of surrounding cells is increased. Locally produced IFN-gamma induces the formation of a fibrotic capsule. Encapsulated MCA can persist virtually life-long in mice without inducing tumors. Together, the foreign body reaction against MCA prevents malignant transformation, probably by reducing DNA damage. This mechanism is more efficient in the presence of IFN-gammaR. Our results indicates that inflammation and scarring, both suspected to contribute to malignancy, prevent cancer in certain situations.
Insights
Inflammation and scarring, part of the foreign body reaction, can prevent cancer by encapsulating carcinogens like methylcholanthrene (MCA). This protective mechanism is more effective with the interferon-gamma receptor (IFN-gammaR).
Area of Science:
- Immunology
- Oncology
- Pathology
Background:
- The foreign body reaction is a fundamental host defense involving inflammation and scarring.
- Chemical carcinogens like methylcholanthrene (MCA) can induce fibrosarcoma and tissue damage.
- The role of the interferon-gamma receptor (IFN-gammaR) in carcinogen-induced tumor development is not fully understood.
Purpose of the Study:
- To investigate the role of the foreign body reaction, particularly the IFN-gammaR pathway, in preventing chemically induced cancer.
- To determine if inflammation and scarring can act as a tumor-preventive mechanism.
Main Methods:
- Induction of fibrosarcoma using methylcholanthrene (MCA) in wild-type and interferon-gamma receptor (IFN-gammaR)-deficient mice.
- Assessment of MCA diffusion, DNA damage, and tumor formation.
- Evaluation of the fibrotic capsule formation and its effect on MCA persistence.
Main Results:
- Tumor development was increased in IFN-gammaR-deficient mice compared to wild-type mice.
- Absence of IFN-gammaR led to increased MCA diffusion and DNA damage.
- IFN-gammaR signaling promoted the formation of a fibrotic capsule, encapsulating MCA and preventing tumor formation.
- Encapsulated MCA persisted long-term without inducing tumors in the presence of IFN-gammaR.
Conclusions:
- The foreign body reaction, specifically the formation of a fibrotic capsule mediated by IFN-gamma, prevents malignant transformation by limiting carcinogen-induced DNA damage.
- Inflammation and scarring, typically associated with cancer promotion, can paradoxically prevent cancer development in certain contexts.
- The IFN-gammaR pathway plays a critical role in this protective foreign body response.
