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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

Changes of cytokines in tumors after DC101 treatment. Comparison of concentrations of interleukin (IL)-6 (A), IL-10 (B), and vascular endothelial growth factor (VEGF) (C) in isolated normal colon tissues and polyps. ns, not significant. *P < 0.05.
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f4-jcp-20-129: Changes of cytokines in tumors after DC101 treatment. Comparison of concentrations of interleukin (IL)-6 (A), IL-10 (B), and vascular endothelial growth factor (VEGF) (C) in isolated normal colon tissues and polyps. ns, not significant. *P < 0.05.

Mentions: As cytokines secreted from immune cells can affect the survival and proliferation of colon adenomas, we first investigated the quantitative changes of IL-6 and IL-10, which have been identified as factors that enhance and suppress the survival of colon tumor cells, respectively, in control and DC101-treated animals.7,12 The concentrations of the two cytokines appeared to be stable in the normal regions of both the untreated and treated animals, but both IL-6 and IL-10 were reduced in the polyps of the treated group compared with the untreated group (Fig. 4A and 4B). The concentration of VEGF in the same tissue homogenate appeared slightly higher in the polyps of the DC101-treated animals (Fig. 4C), indicating the antagonistic function of DC101 against VEGF,13 although the minor concentration difference is not statistically significant.


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

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

Changes of cytokines in tumors after DC101 treatment. Comparison of concentrations of interleukin (IL)-6 (A), IL-10 (B), and vascular endothelial growth factor (VEGF) (C) in isolated normal colon tissues and polyps. ns, not significant. *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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

f4-jcp-20-129: Changes of cytokines in tumors after DC101 treatment. Comparison of concentrations of interleukin (IL)-6 (A), IL-10 (B), and vascular endothelial growth factor (VEGF) (C) in isolated normal colon tissues and polyps. ns, not significant. *P < 0.05.
Mentions: As cytokines secreted from immune cells can affect the survival and proliferation of colon adenomas, we first investigated the quantitative changes of IL-6 and IL-10, which have been identified as factors that enhance and suppress the survival of colon tumor cells, respectively, in control and DC101-treated animals.7,12 The concentrations of the two cytokines appeared to be stable in the normal regions of both the untreated and treated animals, but both IL-6 and IL-10 were reduced in the polyps of the treated group compared with the untreated group (Fig. 4A and 4B). The concentration of VEGF in the same tissue homogenate appeared slightly higher in the polyps of the DC101-treated animals (Fig. 4C), indicating the antagonistic function of DC101 against VEGF,13 although the minor concentration difference is not statistically significant.

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