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Cancers 2010, 2, 970-988; doi:10.3390/cancers2020970 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Review VEGF and Pleiotrophin Modulate the Immune Profile of Breast Cancer Kristi D. Lynn 1, Christina L. Roland 1 and Rolf A. Brekken 1,2,* 1 Division of Surgical Oncology, Department of Surgery; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8593, USA; E-Mails: kristi.lynn@ (K.D.L.); CRolan@ (C.L.R.) 2 Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8593, USA * Author to whom correspondence should be addressed; E-Mail: rolf.brekken@; Tel.: +1-214-648-5151; Fax: +1-214-648-4940. Received: 8 March 2010; in revised form: 13 May 2010 / Accepted: 15 May 2010 / Published: 26 May 2010 Abstract: Angiogenesis, the sprouting of the existing vascular network to form new vessels, is required for the growth of solid tumors. For this reason, the primary stimulant of angiogenesis, vascular endothelial growth factor-A (VEGF), is an attractive target for tumor therapy. In fact, there are currently numerous anti-VEGF therapies in clinical development for the treatment of various cancers, including breast cancer. VEGF signals through two primary VEGF receptors, VEGFR1 and VEGFR2. VEGFR2 is the primary angiogenic receptor, and VEGFR1 has been implicated in macrophage chemotaxis and tumor cell survival and invasion. It ha