We previously established that the trefoil peptides (TFFs) pS2, spasmolytic polypeptide, and intestinal trefoil factor are involved in cellular scattering and invasion in kidney and colonic cancer cells. The hallmark of progression of human colorectal tumors from the early premalignant stages is the acquisition of the invasive phenotype and formation of new blood vessels within the adenomas and adenocarcinomas (1). There is evidence to support a critical role for the inflammatory processes and mucosal ulceration in the emergence of gastrointestinal tumors (2-4). Patients with inflammatory bowel disease have an increased risk of developing intestinal neoplasms. Chronic inflammatory disorders, diabetic retinopathy, tissue ischemia, and tumor angiogenesis are characterized by the branching and sprouting of new blood vessels. The development of solid tumors promotes mobilization of the differentiated endothelium of preexisting vascular cells at the vicinity of the neoplastic tissues and the recruitment of bone marrow-derived endothelial progenitors and hematopoietic stem cells (5-7). Angiogenesis also occurs in healthy individuals during wound healing and other physiologic regulations in the female reproductive tract (8). Several clinical and experimental studies indicate that angiogenesis is critical for the growth and persistence of solid tumors and is strongly associated with the metastatic cascade. The coordinated control of tumor cell invasion, survival, and angiogenesis allows tumor cells to invade distant organs during the complex processes of the metastatic cascade. A tumor mass that is smaller than 0.4 mm in diameter can receive oxygen and nutriments by simple diffusion. However, without surrounding blood vessels, primary colonic tumors 3 mm 3 in size are not able to survive (9). Induction of the angiogenic switch is the consequence of local hypoxia and absolute requirements of growing primary tumors on oxygen, nutriments, and survival factors (9 -11). The formation of new vascular structures during cancer progression is primarily mediated by the proliferation, migration, and morphogenesis of endothelial cells induced by proangiogenic and chemotactic factors stimulating the migratory phenotype through direct and indirect mechanisms involving paracrine and autocrine regulatory loops. Thus, numerous angiogenic factors are produced locally by cancer cells, endothelial cells, and stromal and blood cells. Positive and negative 1 These authors contributed equally to this work.