These experiments demonstrated that tumors formed by Calu6/β2 cells in SCID/NOD mice, either orthotopically or subcutaneously, were significantly smaller following hrIL-12 vs PBS treatment and that the IL-12 mediated anti-tumor activity was primarily due to inhibition of angiogenesis resulting from a complex modulation of the expression of anti-angiogenic (e.g. IFN-α and –β) and pro-angiogenic (e.g. VEGF-C, VEGFR-2, Leptin, PROK2, COX1/COX3, thrombospondin 2) genes. Here, PROK2 is linked to neoplasm.