J Cancer Prev.  2015 Jun;20(2):129-135. 10.15430/JCP.2015.20.2.129.

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

Affiliations
  • 1Department of Pharmacology and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Korea. jinwoochoi@wku.ac.kr
  • 2College of Pharmacy, Catholic University of Daegu, Daegu, Korea.
  • 3Advanced Institute of Convergence Technology, Seoul National University, Suwon, 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.

Keyword

Colon tumorigenesis; Angiogenesis; Antiangiogenic therapy

MeSH Terms

Adenomatous Polyposis Coli
Adenoviridae
Animals
Carcinogenesis
Chemoprevention
Colon*
Cytokines
Interleukin-10
Interleukins
Mice
Mice, Knockout
Receptors, Vascular Endothelial Growth Factor
Recombinases
Vascular Endothelial Growth Factor A
Cytokines
Interleukin-10
Interleukins
Receptors, Vascular Endothelial Growth Factor
Recombinases
Vascular Endothelial Growth Factor A
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