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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

Development of disharmonized region between the Tie2-labeling endothelial cells and perfused vessels during angiogenesis. (A) To induce a colon tumor in the Tie2-green fluorescent protein (GFP) mouse, azoxymethane (AOM, Sigma Aldrich, St. Louis, MO, USA) was injected intraperitoneally at −5 mg/kg. One week later, the mice were given 3% dextran sulfate sodium (DSS; MP Biochemicals, Solon, OH, USA) in drinking water for 5 days, followed by normal drinking water. The colons of the mice were imaged using side-view confocal endomicroscopy at week 8 after the DSS treatment. (B) Intravenously-injected rhodamin-dextran conjugates (500 μg/100 μL, 2,000,000 MW; Invitrogen, Waltham, MA, USA) were used for the imaging of the perfused vessels. The arrows indicate a significantly disharmonized area between the Tie2-GFP and the perfused rhodamin-dextran in the tumor region. Scale bars: 100 μm.
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f1-jcp-20-129: Development of disharmonized region between the Tie2-labeling endothelial cells and perfused vessels during angiogenesis. (A) To induce a colon tumor in the Tie2-green fluorescent protein (GFP) mouse, azoxymethane (AOM, Sigma Aldrich, St. Louis, MO, USA) was injected intraperitoneally at −5 mg/kg. One week later, the mice were given 3% dextran sulfate sodium (DSS; MP Biochemicals, Solon, OH, USA) in drinking water for 5 days, followed by normal drinking water. The colons of the mice were imaged using side-view confocal endomicroscopy at week 8 after the DSS treatment. (B) Intravenously-injected rhodamin-dextran conjugates (500 μg/100 μL, 2,000,000 MW; Invitrogen, Waltham, MA, USA) were used for the imaging of the perfused vessels. The arrows indicate a significantly disharmonized area between the Tie2-GFP and the perfused rhodamin-dextran in the tumor region. Scale bars: 100 μm.

Mentions: As there were several reports that angiogenesis in colon tumorigenesis emerges at an earlier stage compared with other tissues, we confirmed vascular change by monitoring the colon of a single Tie2-GFP mouse after an azoxymethane (AOM) injection. To investigate vascular leakage, we injected rhodamine-dextran into the mouse and performed an image analysis. Irregular changes in the GFP region were observed 4 weeks after the AOM injection, while the vessels were simultaneously perfused with rhodamin fluorescence; the rhodamin region overlapped well with the GFP region to mark the Tie2 expression. Between the two different methods that are commonly used to check vasculature, we found that noticeable differences were exhibited following a single injection of carcinogen that were presumably due to vascular leakage and irregular blood perfusion around the microadenoma (Fig. 1). Our observation is consistent with previous reports that describe abnormal vasculature during tumorigenesis in other genetically engineered mouse models.11


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

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

Development of disharmonized region between the Tie2-labeling endothelial cells and perfused vessels during angiogenesis. (A) To induce a colon tumor in the Tie2-green fluorescent protein (GFP) mouse, azoxymethane (AOM, Sigma Aldrich, St. Louis, MO, USA) was injected intraperitoneally at −5 mg/kg. One week later, the mice were given 3% dextran sulfate sodium (DSS; MP Biochemicals, Solon, OH, USA) in drinking water for 5 days, followed by normal drinking water. The colons of the mice were imaged using side-view confocal endomicroscopy at week 8 after the DSS treatment. (B) Intravenously-injected rhodamin-dextran conjugates (500 μg/100 μL, 2,000,000 MW; Invitrogen, Waltham, MA, USA) were used for the imaging of the perfused vessels. The arrows indicate a significantly disharmonized area between the Tie2-GFP and the perfused rhodamin-dextran in the tumor region. Scale bars: 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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

f1-jcp-20-129: Development of disharmonized region between the Tie2-labeling endothelial cells and perfused vessels during angiogenesis. (A) To induce a colon tumor in the Tie2-green fluorescent protein (GFP) mouse, azoxymethane (AOM, Sigma Aldrich, St. Louis, MO, USA) was injected intraperitoneally at −5 mg/kg. One week later, the mice were given 3% dextran sulfate sodium (DSS; MP Biochemicals, Solon, OH, USA) in drinking water for 5 days, followed by normal drinking water. The colons of the mice were imaged using side-view confocal endomicroscopy at week 8 after the DSS treatment. (B) Intravenously-injected rhodamin-dextran conjugates (500 μg/100 μL, 2,000,000 MW; Invitrogen, Waltham, MA, USA) were used for the imaging of the perfused vessels. The arrows indicate a significantly disharmonized area between the Tie2-GFP and the perfused rhodamin-dextran in the tumor region. Scale bars: 100 μm.
Mentions: As there were several reports that angiogenesis in colon tumorigenesis emerges at an earlier stage compared with other tissues, we confirmed vascular change by monitoring the colon of a single Tie2-GFP mouse after an azoxymethane (AOM) injection. To investigate vascular leakage, we injected rhodamine-dextran into the mouse and performed an image analysis. Irregular changes in the GFP region were observed 4 weeks after the AOM injection, while the vessels were simultaneously perfused with rhodamin fluorescence; the rhodamin region overlapped well with the GFP region to mark the Tie2 expression. Between the two different methods that are commonly used to check vasculature, we found that noticeable differences were exhibited following a single injection of carcinogen that were presumably due to vascular leakage and irregular blood perfusion around the microadenoma (Fig. 1). Our observation is consistent with previous reports that describe abnormal vasculature during tumorigenesis in other genetically engineered mouse models.11

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