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Antiangiogenic Therapy Impedes Infiltration by CD4+ and CD8+ Cells Into an Early Colon Tumor.

Yang YJ, Choi JS, Choi JW - J Cancer Prev (2015)

Bottom Line: Furthermore, the administration of the VEGF antagonist decreased the amounts of anti-tumoral cytokines such as interleukin (IL)-6 and IL-10.We revealed that newly formed vessels during tumorigenesis can be channels for particular anti-tumoral immune cells.Our results may confer insight for the clinical development of an efficient antiangiogenic therapeutic manual and a timely chemoprevention to suppress tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Korea.

ABSTRACT

Background: While the majority of angiogenesis studies have focused on the late stages of cancer, the emergence of neovascularization in colon tumorigenesis has been observed an earlier stage than expected. Recent reports implied that early angiogenesis might be a defense mechanism to stimulate the natural clearance of microadenomas during colon tumorigenesis. However, little is known about how early angiogenesis affects the natural clearance of tumors.

Methods: Spontaneous colon tumors were developed in adenomatous polyposis coli conditional knockout mice with Cre recombinase adenovirus administration. Vascular endothelial growth factor (VEGF) antagonist, DC101, was administrated to determine the effect of early angiogenesis and then infiltration of immune cells into tumor and concentration of cytokines were evaluated.

Results: The continuous administration of the VEGF receptor 2 antagonist DC101 in the mouse models impeded the infiltration by CD4+ and CD8+ cells into the tumor region. Furthermore, the administration of the VEGF antagonist decreased the amounts of anti-tumoral cytokines such as interleukin (IL)-6 and IL-10.

Conclusions: We revealed that newly formed vessels during tumorigenesis can be channels for particular anti-tumoral immune cells. Our results may confer insight for the clinical development of an efficient antiangiogenic therapeutic manual and a timely chemoprevention to suppress tumor growth.

No MeSH data available.


Related in: MedlinePlus

Reduction of infiltration by various immune cells into adenomas after DC101 treatment. (A) The mice were intraperitoneally injected with DC101 (40 mg/kg) once every 3 days for 4 weeks, and the colons were isolated and fixed with 10% formalin. For immunofluorescent staining, the tissues were blocked with 3% H2O2 in methanol to inactivate the endogenous peroxidases. The slides were firstly washed with phosphate-buffered saline and incubated for 20 minutes in a protein-blocking solution supplemented with 4% normal bovine serum albumin; the slides were then incubated overnight at 4°C with primary antibodies against F4/80, CD11c, CD335, CD4, and CD8 (upper panel). (B) The cell count was determined from four independent images with a 20× objective field of view (FOV) before it was statistically analyzed. Scale bar, 100 μm. ns, not significant. *P < 0.05.
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f3-jcp-20-129: Reduction of infiltration by various immune cells into adenomas after DC101 treatment. (A) The mice were intraperitoneally injected with DC101 (40 mg/kg) once every 3 days for 4 weeks, and the colons were isolated and fixed with 10% formalin. For immunofluorescent staining, the tissues were blocked with 3% H2O2 in methanol to inactivate the endogenous peroxidases. The slides were firstly washed with phosphate-buffered saline and incubated for 20 minutes in a protein-blocking solution supplemented with 4% normal bovine serum albumin; the slides were then incubated overnight at 4°C with primary antibodies against F4/80, CD11c, CD335, CD4, and CD8 (upper panel). (B) The cell count was determined from four independent images with a 20× objective field of view (FOV) before it was statistically analyzed. Scale bar, 100 μm. ns, not significant. *P < 0.05.

Mentions: We then conducted an immunohistological investigation of the infiltration by tumor-related immune cells into the colon tumor upon the commencement of DC101 treatment. The numbers of F4/80+ macrophages, CD11c+ dendritic cells, and CD335+ NK cells were similar between the untreated and treated groups, whereas the CD4+ and CD8+ cell counts were modestly lower in the treated group (Fig. 3). Considering the critical role of the CD4+ cell subpopulation in the tumorigenesis of colon cancer, the reduction of the CD4+ cell count from DC101 treatment might therefore contribute to the treatment’s tumor-suppressing effect.


Antiangiogenic Therapy Impedes Infiltration by CD4+ and CD8+ Cells Into an Early Colon Tumor.

Yang YJ, Choi JS, Choi JW - J Cancer Prev (2015)

Reduction of infiltration by various immune cells into adenomas after DC101 treatment. (A) The mice were intraperitoneally injected with DC101 (40 mg/kg) once every 3 days for 4 weeks, and the colons were isolated and fixed with 10% formalin. For immunofluorescent staining, the tissues were blocked with 3% H2O2 in methanol to inactivate the endogenous peroxidases. The slides were firstly washed with phosphate-buffered saline and incubated for 20 minutes in a protein-blocking solution supplemented with 4% normal bovine serum albumin; the slides were then incubated overnight at 4°C with primary antibodies against F4/80, CD11c, CD335, CD4, and CD8 (upper panel). (B) The cell count was determined from four independent images with a 20× objective field of view (FOV) before it was statistically analyzed. Scale bar, 100 μm. ns, not significant. *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4492357&req=5

f3-jcp-20-129: Reduction of infiltration by various immune cells into adenomas after DC101 treatment. (A) The mice were intraperitoneally injected with DC101 (40 mg/kg) once every 3 days for 4 weeks, and the colons were isolated and fixed with 10% formalin. For immunofluorescent staining, the tissues were blocked with 3% H2O2 in methanol to inactivate the endogenous peroxidases. The slides were firstly washed with phosphate-buffered saline and incubated for 20 minutes in a protein-blocking solution supplemented with 4% normal bovine serum albumin; the slides were then incubated overnight at 4°C with primary antibodies against F4/80, CD11c, CD335, CD4, and CD8 (upper panel). (B) The cell count was determined from four independent images with a 20× objective field of view (FOV) before it was statistically analyzed. Scale bar, 100 μm. ns, not significant. *P < 0.05.
Mentions: We then conducted an immunohistological investigation of the infiltration by tumor-related immune cells into the colon tumor upon the commencement of DC101 treatment. The numbers of F4/80+ macrophages, CD11c+ dendritic cells, and CD335+ NK cells were similar between the untreated and treated groups, whereas the CD4+ and CD8+ cell counts were modestly lower in the treated group (Fig. 3). Considering the critical role of the CD4+ cell subpopulation in the tumorigenesis of colon cancer, the reduction of the CD4+ cell count from DC101 treatment might therefore contribute to the treatment’s tumor-suppressing effect.

Bottom Line: Furthermore, the administration of the VEGF antagonist decreased the amounts of anti-tumoral cytokines such as interleukin (IL)-6 and IL-10.We revealed that newly formed vessels during tumorigenesis can be channels for particular anti-tumoral immune cells.Our results may confer insight for the clinical development of an efficient antiangiogenic therapeutic manual and a timely chemoprevention to suppress tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Korea.

ABSTRACT

Background: While the majority of angiogenesis studies have focused on the late stages of cancer, the emergence of neovascularization in colon tumorigenesis has been observed an earlier stage than expected. Recent reports implied that early angiogenesis might be a defense mechanism to stimulate the natural clearance of microadenomas during colon tumorigenesis. However, little is known about how early angiogenesis affects the natural clearance of tumors.

Methods: Spontaneous colon tumors were developed in adenomatous polyposis coli conditional knockout mice with Cre recombinase adenovirus administration. Vascular endothelial growth factor (VEGF) antagonist, DC101, was administrated to determine the effect of early angiogenesis and then infiltration of immune cells into tumor and concentration of cytokines were evaluated.

Results: The continuous administration of the VEGF receptor 2 antagonist DC101 in the mouse models impeded the infiltration by CD4+ and CD8+ cells into the tumor region. Furthermore, the administration of the VEGF antagonist decreased the amounts of anti-tumoral cytokines such as interleukin (IL)-6 and IL-10.

Conclusions: We revealed that newly formed vessels during tumorigenesis can be channels for particular anti-tumoral immune cells. Our results may confer insight for the clinical development of an efficient antiangiogenic therapeutic manual and a timely chemoprevention to suppress tumor growth.

No MeSH data available.


Related in: MedlinePlus