Figure 1.

Intravenous injection of neuroendocrine (NE) cell alone generates liver metastasis, while co-injection of NE and mesenchymal-like (NonNE) tumor cells into the bloodstream also causes frequent mediastinal metastasis and occasional lung metastasis. NonNE tumor cells in subcutaneously transplanted mice are crucial for the invasion capacity of NE tumor cells (Top). Fgf2 secreted by NonNE cells induces Pea3 expression via MAPK activation in NE cells. Pea3 induction is required for the metastasis of NE cells. NonNE cells also secrete extracellular matrix (ECM) remodeling factors such as LOX, Cathepsin, and PAI-1. These ECM modifiers likely further facilitate metastasis of SCLC (Bottom).