Related Experiment Video
Updated: Jun 25, 2026
Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Dysregulation of CXCL9 and reduced tumor growth in Egr-1 deficient mice
Giuseppe Caso1, Catherine Barry, Gerald Patejunas
1Department of Surgery, Stony Brook University, Stony Brook, NY, USA.giuseppe.caso@stonybrook.edu
Background:
Early growth response-1 (Egr-1) is an immediate-early transcription factor inducible in the vasculature in response to injury, shear stress, and other stimuli. Mice lacking Egr-1 have a profound deficit in the ability to recover from femoral artery ligation, suggesting a role in neovascularization. Previous studies have shown that manipulating Egr-1 expression can have either positive or negative effects on tumor growth. We hypothesized that Egr-1 knockout mice might exhibit reduced tumor growth, possibly due to a reduced capacity to respond to angiogenic signals from a growing tumor.
Results:
We injected 106 Lewis lung carcinoma (LLC1) cells subcutaneously in the flank of wild type and Egr-1 knockout mice. The average mass of tumors from wild type mice at 12 days after implantation was 413 +/- 128 mg, while those from Egr-1-/- mice was 219 +/- 81 mg (p = 0.001, mean +/- SD). However, sectioning the tumors and staining with anti-CD31 antibodies revealed no difference in the vascularity of the tumors and there was no difference in angiogenic growth factor expression. Expression of the chemokine Mig (CXCL9) was increased 2.8-fold in tumors from knockout mice, but no increase was found in serum levels of Mig. Natural killer cells have a 1.7-fold greater prevalence in the CD45+ cells found in tumors from Egr-1-/- mice compared to those from wild type mice. Immunohistochemical staining suggests that Mig expression in the tumors comes from invading macrophages.
Conclusion:
Mice deficient in Egr-1 exhibit reduced growth of LLC1 tumors, and this phenomenon is associated with overexpression of Mig locally within the tumor. There are no obvious differences in tumor vascularity in the knockout mice. Natural killer cells accumulate in the tumors grown in Egr-1-/- mice, providing a potential mechanism for the reduction in growth.
Insights
Mice lacking Early growth response-1 (Egr-1) showed significantly reduced tumor growth. This was linked to increased Mig chemokine expression and natural killer cell accumulation within tumors, not altered vascularity.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Early growth response-1 (Egr-1) is a transcription factor involved in vascular responses to stimuli.
- Egr-1 plays a role in neovascularization and has complex effects on tumor growth.
- Egr-1 knockout mice exhibit impaired recovery from vascular injury.
Purpose of the Study:
- To investigate the role of Egr-1 in tumor growth.
- To determine if Egr-1 deficiency reduces tumor growth by affecting angiogenesis or immune response.
Main Methods:
- Subcutaneous injection of Lewis lung carcinoma (LLC1) cells into wild type and Egr-1 knockout mice.
- Tumor mass measurement, CD31 staining for vascularity, and analysis of angiogenic growth factor and chemokine expression.
- Flow cytometry and immunohistochemistry to assess immune cell infiltration and chemokine source.
Main Results:
- Egr-1 knockout mice exhibited significantly reduced LLC1 tumor mass compared to wild type mice.
- No significant differences were observed in tumor vascularity or angiogenic growth factor expression.
- Tumors in Egr-1 knockout mice showed increased expression of the chemokine Mig (CXCL9) and a higher prevalence of natural killer cells.
Conclusions:
- Egr-1 deficiency leads to reduced LLC1 tumor growth.
- Overexpression of Mig within the tumor microenvironment is associated with reduced tumor growth in Egr-1 deficient mice.
- Accumulation of natural killer cells in tumors may contribute to the observed reduction in tumor growth.
