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Three-dimensional changes in lymphatic architecture around VX2 tongue cancer--dynamic changes after administration of
1First Department of Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University, Morioka, Japan. akifuji@iwate-med.ac.jp
Abstract:
We examined the three-dimensional changes of the lymphatic architecture in the rabbit VX2 tongue cancer model after administration of an antiangiogenic agent, TNP-470. TNP-470 at 30 mg/kg was administered via the auricular vein to the rabbit four times every other day from 3 days after transplantation of the tumor. The tongue and both sides of deep cervical lymph nodes of rabbit were observed at 10 days after transplantation. Lymph node metastasis was confirmed histopathologically. Morphological changes of collecting lymphatic vessels and lymphatic capillaries were observed, and the number and diameter of lymphatic vessels within 500 microm around the tumor were measured using the combined method with 5'-nucleotidase staining and three-dimensional reconstruction imaging. Tumor growth and lymph node metastasis were suppressed by administration of TNP-470. In the TNP-treatment group, the mean number of lymphatic capillaries was significantly fewer than in the control group. The mean diameter of collecting lymphatic vessels was significantly smaller than in the control group. In conclusion, our results suggest that cancer cell invasion into the lymphatics is probably decreased by inhibiting not only the growth of tumor but also new formation of lymphatic capillaries around the tumor by administration of TNP-470.
Insights
Antiangiogenic agent TNP-470 reduced tumor growth and lymph node metastasis in rabbits. This drug therapy decreased lymphatic capillaries and collecting lymphatic vessel diameter, suggesting reduced cancer cell invasion.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Research
Background:
- Tumor growth and metastasis are significantly influenced by the lymphatic system.
- Antiangiogenic agents show promise in cancer therapy by targeting tumor vasculature.
- Understanding the impact of antiangiogenic therapy on lymphatic architecture is crucial for improving treatment strategies.
Purpose of the Study:
- To investigate the three-dimensional changes in lymphatic architecture following TNP-470 administration in a rabbit VX2 tongue cancer model.
- To evaluate the effect of TNP-470 on tumor growth, lymph node metastasis, and lymphatic vessel morphology.
Main Methods:
- VX2 tongue cancer model established in rabbits.
- Administration of TNP-470 (30 mg/kg) via auricular vein over eight days.
- Histopathological examination of tongue tumors and deep cervical lymph nodes.
- 3D reconstruction imaging combined with 5'-nucleotidase staining to analyze lymphatic capillaries and collecting lymphatic vessels.
Main Results:
- TNP-470 significantly suppressed tumor growth and lymph node metastasis.
- The number of lymphatic capillaries within 500 microm of the tumor was significantly reduced in the TNP-470 treated group.
- The mean diameter of collecting lymphatic vessels was significantly smaller in the TNP-470 treated group compared to controls.
Conclusions:
- TNP-470 inhibits both tumor growth and the formation of new lymphatic capillaries around the tumor.
- These effects likely contribute to decreased cancer cell invasion into the lymphatics.
- Targeting lymphangiogenesis with agents like TNP-470 may represent a viable strategy to prevent cancer metastasis.
