Vascular endothelial growth factor-C induces lymphangitic carcinomatosis, an extremely aggressive form of lung metastases.

The lymphatic system is an important pathway for tumor dissemination to the lymph nodes, but to which extent it contributes to the formation of distant metastases remains unknown. We report that induction of lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) at the secondary site, in the lung, facilitates expansion of already disseminated cancer cells throughout the lung tissue. By using orthotopic spontaneous metastasis models in nude mice, we show that VEGF-C expression by tumor cells altered the pattern of pulmonary metastases from nodular to diffuse and facilitated disease progression.

Heterogeneity of EAE mediated by multiple distinct T-effector subsets.

Both T(H)1 and T(H)17 lymphocytes are implicated in inducing EAE. In mice lacking IFNgamma, T(H)17 are assumed to be the subset responsible for inflammation induction. Here, we demonstrate that IFNgamma KO mice have two additional effector subsets, one that up-regulates T(H)17-associated pro-inflammatory genes, but does not make IL-17 protein, and a second that utilizes IL-12-related elements of the T(H)1 pathway in an IFNgamma-independent manner.