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Updated: Jul 16, 2026
In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
A study of dendritic and endothelial cell interactions in colon cancer in a cell line and small mammal model
S Yoneyama1, Y Okaji, N H Tsuno
1Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. yoneyamas-tky@umin.ac.jp
Aim:
Historically, cancer therapy directly targeting tumor cells have yielded suboptimal clinical results, and therefore anti-angiogenic therapy that targets tumor cells indirectly through impairing tumor vasculature is now considered to be one of the novel approaches potentially effective against various types of cancer. In this study, we evaluated whether lysates of endothelium could be effectively pulsed in dendritic cells (DCs), to enhance their anti-tumor effects.
Methods:
For this purpose, we prepared DCs of BALB/c mouse, incubated them with lysates of autologous or xenogeneic endothelium, and tested their anti-tumor effects in two syngeneic models of colon cancer.
Results:
DCs pulsed with the respective endothelium lysates significantly inhibited the growth of subcutaneous tumors as well as pulmonary metastases in mice, and their anti-tumor effect was superior to that of unpulsed DCs. Immunohistopathological analysis showed significant decrease in the mean vascular density of tumors, correlating well with the extent of tumor inhibition. In vitro analysis of splenocytes isolated from immunized mice revealed an induction of cytotoxic T lymphocytes and activation of natural killer cells, with a lytic activity against activated endothelium but not tumor cells. In addition, antibodies reacting with activated endothelium, but not tumor cells, were detected in murine sera by ELISA, and their function was confirmed by complement-dependent cytotoxicity assay.
Conclusions:
Our present results suggest that lysates of endothelium can be effectively pulsed in DCs and enhance their anti-tumor effects through induction of anti-angiogenesis, and therefore should have important clinical implications for adjuvant cancer therapy.
Insights
This study shows that pulsing dendritic cells (DCs) with endothelium lysates enhances anti-tumor effects by inducing anti-angiogenesis. This approach offers a promising strategy for improving cancer therapy outcomes.
Area of Science:
- Immunology
- Oncology
- Vascular Biology
Background:
- Conventional cancer therapies targeting tumor cells directly have limited efficacy.
- Anti-angiogenic therapy, targeting tumor vasculature, is a promising alternative cancer treatment strategy.
- Dendritic cells (DCs) are potent antigen-presenting cells that can be engineered for cancer immunotherapy.
Purpose of the Study:
- To investigate the potential of using endothelium lysates to enhance the anti-tumor effects of dendritic cells (DCs).
- To evaluate the anti-angiogenic and anti-tumor efficacy of DCs pulsed with endothelium lysates.
Main Methods:
- Prepared DCs from BALB/c mice and incubated them with autologous or xenogeneic endothelium lysates.
- Assessed anti-tumor effects in syngeneic colon cancer models.
- Performed immunohistopathology, splenocyte analysis, ELISA, and complement-dependent cytotoxicity assays.
Main Results:
- DCs pulsed with endothelium lysates significantly inhibited tumor growth and pulmonary metastases.
- Reduced mean vascular density in tumors correlated with tumor inhibition.
- Induced cytotoxic T lymphocytes and activated natural killer cells, with antibodies targeting activated endothelium.
Conclusions:
- Endothelium lysates can be effectively pulsed into DCs to enhance anti-tumor effects.
- The mechanism involves the induction of anti-angiogenesis.
- This approach holds significant clinical implications for adjuvant cancer therapy.
