Endogenous galectin-3 expression levels modulate immune responses in galectin-3 transgenic mice
Aparna D Chaudhari1, Rajiv P Gude2, Rajiv D Kalraiya2
1Chiplunkar Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai 410210, Maharashtra, India.
Molecular Immunology
|October 8, 2015
Summary
Complete absence of galectin-3 (Gal-3) in mice enhances melanoma lung metastasis by impairing Natural Killer (NK) cell function and disrupting immune signaling pathways. This highlights Gal-3
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Galectin-3 (Gal-3) is a mammalian lectin implicated in cancer progression and metastasis.
- The precise role of endogenous Gal-3 in regulating host immunity and cancer metastasis remains incompletely understood.
- Gal-3 is recognized as a key modulator of immune responses.
Purpose of the Study:
- To investigate how endogenous galectin-3 expression influences host immunity and lung metastasis in a B16F10 murine melanoma model.
- To elucidate the mechanisms by which galectin-3 modulates immune cell function and cytokine profiles.
- To determine the impact of galectin-3 deficiency on melanoma cell metastasis in vivo.
Main Methods:
- Utilized transgenic Gal-3(+/-) and Gal-3(-/-) mice alongside wild-type Gal-3(+/+) controls.
- Assessed Natural Killer (NK) cell levels and cytotoxicity against YAC-1 tumor targets.
- Analyzed T cell proliferation, intracellular calcium flux, and serum cytokine levels (Th1, Th2, Th17, IFN-γ).
- Investigated IFN-γ signaling pathway components, including IFN-γR1, SOCS1, SOCS3, and STAT1.
- Quantified B16F10 melanoma lung metastasis formation in different mouse genotypes.
Main Results:
- Gal-3(-/-) mice showed reduced NK cell levels and cytotoxicity compared to wild-type mice.
- T cell proliferation was increased in Gal-3(+/-) and Gal-3(-/-) mice, but with lower calcium flux in Gal-3(-/-) T cells.
- Gal-3(-/-) mice exhibited dysregulated serum cytokine profiles, with lowest Th1, Th2, and Th17 levels, and decreased IFN-γ.
- IFN-γ signaling appeared attenuated in Gal-3(-/-) mice, evidenced by higher SOCS1/SOCS3 expression.
- B16F10 lung metastasis was comparable in Gal-3(+/+) and Gal-3(-/-) mice, but reduced in Gal-3(+/-) mice.
Conclusions:
- Complete absence of endogenous galectin-3 (Gal-3) facilitates B16F10 melanoma lung metastasis in mice.
- This facilitation is likely due to dysregulated immune responses, including decreased NK cell cytotoxicity and altered cytokine milieu.
- Impaired IFN-γ signaling via the STAT1 pathway in Gal-3(-/-) mice may contribute to enhanced metastasis.
- Partial deficiency (Gal-3(+/-)) appears to have a protective effect against metastasis in this model.
