Lymphatic mapping of mice with systemic lymphoproliferative disorder: usefulness as an inter-lymph node metastasis model of cancer.

Preclinical models of lymph node (LN) metastasis are fundamental to the study and design of new techniques for the diagnosis and treatment of LN metastasis. However, the identification of LNs and lymphatic vessels (LVs) in mice is challenging with conventional imaging modalities, since the LN diameter in normal mice is 1-2 mm. Here, we describe MXH10/Mo-lpr/lpr (MXH10/Mo/lpr) inbred mice, which develop systemic swelling of LNs up to 10 mm in diameter, allowing investigation of the topography of LNs and LVs. Using a gross anatomy dissection approach, we identified 22 different LNs situated in the head and neck, limbs, thoracic and abdominal regions. Furthermore, four peripheral inter-LN vessels were found: from the subiliac LN (SiLN) to the proper axillary LN (PALN); from the parotid LN to the caudal deep cervical LN; and from the popliteal LN to both the sciatic LN and the SiLN. Metastasis to the PALN via LVs was induced by inoculating FM3A/Luc mouse mammary carcinoma cells into the SiLN. Our results demonstrate that the MXH10/Mo/lpr mouse strain is an excellent model in which to investigate lymphatic drainage and inter-LN metastasis of cancer. This paper unveils the anatomy of murine lymphatics to give new insights into the investigation of inter-LN metastasis of cancer, especially the mechanisms involved in the trafficking of cancer cells through inter-LN vessels. The results provide data that may prove very useful in the quest to develop better lymph drainage-based drug delivery systems.

Photothermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light.

Lymph node dissection for regional nodal metastasis is a primary option, but is invasive and associated with adverse effects. The development of non-invasive therapeutic methods in preclinical experiments using mice has been restricted by the small lymph node size and the limited techniques available for non-invasive monitoring of lymph node metastasis. Here, we show that photothermal therapy (PTT) using gold nanorods (GNRs) and near-infrared (NIR) laser light shows potential as a non-invasive treatment for tumors in the proper axillary lymph nodes (proper-ALNs) of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes (up to 13mm in diameter, similar in size to human lymph nodes). Tumor cells were inoculated into the proper-ALNs to develop a model of metastatic lesions, and any anti-tumor effects of therapy were assessed. We found that GNRs accumulated in the tumor in the proper-ALNs 24h after tail vein injection, and that irradiation with NIR laser light elevated tumor temperature. Furthermore, combining local or systemic delivery of GNRs with NIR irradiation suppressed tumor growth more than irradiation alone. We propose that PTT with GNRs and NIR laser light can serve as a new therapeutic method for lymph node metastasis, as an alternative to lymph node dissection.