Additionally, chronic restraint stress promoted angio- and lymphangiogenesis [49, 69] and the reorganisation of lymphatic networks within and around the primary tumor via induction of tumor-derived vascular endothelial growth factor C (VEGF-C), which in turn was found to depend on cyclooxygenase-2 (COX-2) mediated inflammatory signaling from macrophages [69]. Here, PTGS2 is linked to neoplasm.