Lymph Metastasis

The spread of cancer cells from the primary tumor to the lymph nodes is a critical event in disease progression that determines the overall prognosis for the patient and the course of therapy to be administered. The mechanisms used by cancer cells to form lymph node metastasis are starting to be understood, with the hope of identifying treatment strategies to lower mortality due to disseminated cancer.

In contrast to hematogenous metastasis in which the primary tumor has functional blood vessels for cancer cells to invade, the story for lymphatic metastasis is likely more complicated. Solid tumors seem to lack functional intratumor lymphatic vessels {Padera, 2002 #14} (see Solid Stress) for one reason), which means tumor cells that enter intratumor lymphatic vessels will not be carried by lymph flow to lymph nodes. This route for dissemination is therefore highly inefficient, at best. Tumor cells can be visualized moving in lymphatic vessels in our novel animal models.

If intratumor lymphatic vessels are not efficient routes for lymphatic dissemination, how then do lymph node metastases occur? Functional lymphatic vessels in the margin of tumors are sufficient for lymphatic metastasis to occur {Padera, 2002 #14}. These functional tumor margin lymphatics may be passive victims of tumor cell invasion or they may play an active role in attracting tumor cells to them. In addition, these lymphatics respond to tumor secreted lymphangiogenic molecules vascular endothelial growth factor (VEGF) C {Hoshida, 2006 #16; Padera, 2002 #14}, causing lymphatic vessel sprouting and hyperplasia in the tumor margin.

The increase in the total surface area of lymphatic vessels provides more opportunities for tumor cell invasion. Indeed, we have shown an increase in tumor cell arrival from tumors with VEGF-C induced lymphatic hyperplasia.