Sep 15, 2019

Use of a Lymphatic Drug Delivery System and Sonoporation to Target Malignant Metastatic Breast Cancer Cells Proliferating in the Marginal Sinuses

Scientific Reports
Shigeki KatoTetsuya Kodama

Abstract

Lymph node (LN) metastasis through the lymphatic network is a major route for cancer dissemination. Tumor cells reach the marginal sinuses of LNs via afferent lymphatic vessels (LVs) and form metastatic lesions that lead to distant metastasis. Thus, targeting of metastatic cells in the marginal sinuses could improve cancer treatment outcomes. Here, we investigated whether lymphatic administration of a drug combined with sonoporation could be used to treat a LN containing proliferating murine FM3A breast cancer cells, which are highly invasive, in its marginal sinus. First, we used contrast-enhanced high-frequency ultrasound and histopathology to analyze the structure of LVs in MXH10/Mo-lpr/lpr mice, which exhibit systemic lymphadenopathy. We found that contrast agent injected into the subiliac LN flowed into the marginal sinus of the proper axillary LN (PALN) and reached the cortex. Next, we examined the anti-tumor effects of our proposed technique. We found that a strong anti-tumor effect was achieved by lymphatic administration of doxorubicin and sonoporation. Furthermore, our proposed method prevented tumor cells in the marginal sinus from invading the parenchyma of the PALN and resulted in tumor necrosis. We conclude that l...Continue Reading

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Mentioned in this Paper

Doxorubicin
Set of Afferent Lymphatic Vessels
Biological Neural Networks
Parenchyma
Neoplastic Cell
Murine
Lymphadenopathy
Administration Procedure
Anatomical Space Structure
Lymph Nodes

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