Model on the contribution of TNFα, VEGF and COX-2 to melanoma metastasis-stimulating effects of bacterial endotoxin-activated bone marrow stromal cells. TNFα production from LPS-activated BMSCs induces VEGF production and VCAM-1 expression from BMSCs. BMSC-derived TNFα can also stimulate VEGF production from TNF receptor-expressing melanoma cells via COX-2-dependent mechanism. Next, those TNF receptor-expressing and non-TNF receptor-expressing melanoma cells that express VEGF receptors increase proliferation and VLA-4-dependent adhesion to BMSCs via COX-2-dependent mechanism. Therefore, two antimetastatic intervention sites for COX-2 inhibitors may exist in the prometastatic microenvironment generated by endotoxin-activated bone marrow stromal cells.