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Updated: May 4, 2026
A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
Mice lacking NCF1 exhibit reduced growth of implanted melanoma and carcinoma tumors
Tiina Kelkka1, Angela Pizzolla2, Juha Petteri Laurila3
1Medicity Research Laboratory, Turku, Finland ; Turku Doctoral Programme of Biomedical Sciences, Turku, Finland.
Abstract:
The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1 (m1J) mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1 (m1J) mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1 (m1J) mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors.
Insights
Mice lacking the NADPH oxidase 2 (NOX2) complex showed reduced tumor growth in models of antigenic tumors. Reactive oxygen species (ROS) appear crucial for rejecting certain tumors, but not for intrinsically generated ones.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- The NADPH oxidase 2 (NOX2) complex generates reactive oxygen species (ROS), vital for immunity.
- The role of NOX2-derived ROS in cancer development is not fully understood.
- Phagocytes are primary sites of NOX2 expression and ROS production.
Purpose of the Study:
- To investigate the role of the NOX2 complex and ROS in tumor development across different cancer models.
- To compare tumor growth in wild-type mice versus mice lacking a functional NOX2 complex (Ncf1 (m1J) mutated mice).
Main Methods:
- Utilized four distinct tumor models: B16 melanoma (with FLT3L or luciferase), Lewis Lung Carcinoma (LLC), and TRAMP prostate carcinoma.
- Compared tumor development and growth rates between wild-type and Ncf1 (m1J) mutated mice.
- Analyzed associated immune responses, including cytokine production.
Main Results:
- Ncf1 (m1J) mice exhibited significantly smaller tumors in two melanoma models (B16-FLT3L and B16-luc).
- Fewer LLC tumors developed in Ncf1 (m1J) mice, though those that formed grew similarly to controls.
- Prostate tumor growth in TRAMP mice was unaffected by the lack of NOX2 function.
- Absence of ROS was linked to increased pro-inflammatory cytokines, particularly Th2 cytokines in the LLC model.
Conclusions:
- Reactive oxygen species (ROS) generated by the NOX2 complex play a role in the rejection of antigenic tumors (B16-luc, LLC).
- ROS do not appear to influence the growth of intrinsically generated tumors (TRAMP).
- The findings suggest a complex interplay between ROS, immune responses, and tumor rejection.
