"The Role of B Cells in Tumor-Induced Lymph Node Lymphangiogenesis and Lymphatic Metastasis"
Cancer metastasis is responsible for more than 90% of human cancer deaths. Identifying major players and understanding the molecular mechanism of metastasis are thus critical to the development of effective anti-cancer therapies.
Tumor cells can spread to distant organs via the blood or the lymphatic system, yet most investigations of the mechanism of metastasis have focused on tumor spread through the blood. We have recently shown that the lymphatic system is the preferential route of melanoma metastasis. Regional tumor-draining lymph nodes (TDLNs) are often the first organs to develop metastases. Histological detection of metastatic tumor cells in TDLNs of cancer patients therefore serves as the major diagnostic method in clinical oncology to assess tumor metastatic potential and to determine the best therapeutic regimen for the patient. These findings solidify the need to understand the mechanism of tumor metastasis through the lymphatic system.
We are especially interested in the TDLN microenvironment, as tumor metastasis is preceded by TDLN lymphatic sinus growth (lymphangiogenesis), increased lymph flow, and increased number of B cells within the TDLN. Furthermore, in the absence of B cells but not T cells, LN lymphangiogenesis is prevented, with no signs of subsequent metastasis. These studies strongly suggest that B cell accumulation in the TDLN is required for LN lymphangiogenesis and metastasis.
We aim to determine the molecular mechanism of B cell accumulation in TDLNs and how B cells facilitate lymphatic metastasis. Findings from these studies may reveal potential therapeutic targets to prevent B cell accumulation and metastasis.