In their latest study, Krygier and Djakiew (pages 1–7) demonstrate a role for p75NTR in the suppression of NGF-stimulated metastasis of human prostate cancer cells. Several growth factors and their receptors have been implicated in the progression from human prostate epithelial cells to metastatic prostate cancer, including nerve growth factor (NGF) and its corresponding neurotrophin receptor, p75NTR. The receptor belongs to the tumor necrosis factor receptor superfamily and is able to induce apoptosis in various tissues and cell lines. Djakiew's group previously showed recently that p75NTR expression is progressively lost during the malignant transformation of prostate tissue. In the work reported in this issue, the expression of p75NTR inhibited the NGF-induced formation of satellite tumors in SCID mice carrying primary prostate tumors. Exactly how p75NTR prevents single cells from cutting their ties and then migrating along perineural routes, their usual mode of dissemination, remains to be elucidated. Satellite tumor formation in SCID mice. Multiple pathways influence tumor vascularization, but among many endothelial regulators, vascular endothelial growth factor (VEGF) has been characterized as the most potent stimulus of angiogenesis in human carcinomas. Not surprisingly, VEGF status proved to be a significant prognostic indicator in many solid tumors. But a naturally occurring soluble form of its receptor, sVEGFR1, can mop up VEGF and slow tumor progression, according to a new report by Toi et al. (pages 14–18). Their study examines sVEGFR1 levels in primary breast cancer tissue and for the first time assesses its clinical significance with respect to VEGF levels. They show not only that sVEGFR1 is frequently co-expressed with VEGF, but also that tumors in which soluble receptor levels exceed those of the ligand at least 10-fold have a markedly favorable prognosis. This result ties in nicely with several reports indicating that the balance between positive and negative players is more important than absolute levels of individual regulators. Further investigation is necessary to clarify the clinical importance of this particular negative player in other types of cancer. Relapse free survival stratified by sVEGFR1/VEGF. Tumors with S/V ratio >10 have a significantly favorable prognosis compared to those with S/V ≤10. Van Broekhoven and Altin (pages 63–72) have developed a simple and fast approach to creating custom-made anti-tumor vaccines based on tumor cell-derived plasma membrane vesicles. Cancer vaccines have come a long way: from crude tumor lysates to sophisticated, genetically tweaked cell hybrids expressing specific tumor antigens, cell surface costimulatory molecules and/or immunostimulatory cytokines. Despite the potential therapeutic benefits of using such genetically modified tumor cells, both technical feasibility and safety concerns limit their use as vaccines in clinical settings. To address this problem, Van Broekhoven and Altin inserted NTA-anchors covalently linked to lipid molecules, in the membrane of their vesicles, and attached histidine-tagged costimulatory molecules such as B7.1 and CD 40 to specifically enhance anti-tumor immune responses. This method also allows the simultaneous encapsulation of immunostimulatory cytokines such as IL-2, ensuring their targeted delivery and thus giving T cell proliferation an additional boost. Promising first results have been found in a mouse tumor model by modifying vesicles in this manner. But most importantly this approach will provide a quick and straightforward system to test a range of surface molecules, cytokines, cancer drugs and various proteins, peptides and DNA for their contribution to the optimal cancer vaccine. Expression of multidrug resistance protein 1 (MRP1), a member of the ABC transporter family, confers chemoresistance to neuroblastoma and is associated with a poor prognosis. In this issue, Kuss et al. (pages 128–133) describe a possible way to overcome this hurdle: the use of antisense oligonucleotides to transiently downregulate expression of specific genes. The potential of this method as an effective cancer therapy is being widely investigated at the moment. Induction of tumor immunity by immunization with PMV containing encapsulated IL-2 and engrafted with recombinant costimulatory molecules. Kuss and his colleagues treated mice carrying human neuroblastoma xenografts with MRP1 antisense oligonucleotides and could reduce MRP1 protein levels by an average of 40 percent. This treatment sensitized the tumor cells to etoposide. But surprisingly, the downregulation of MRP1 increased apoptotic cell death by an impressive 79 percent and simultaneously decreased the mitotic index by 42 percent prior to any cytotoxic chemotherapy. The authors conclude that, apart from its function as a drug-resistance pump, MRP1 plays an additional role in the prognostic outcome by influencing cell death rates and proliferation of neuroblasts. The next step will be to elucidate the tactics the multitalented MRP1 employs to promote tumor growth. Effects of antisense oligonucleotide treatment on apoptotic index scores of IMR32 neuroblastoma tumors relative to untreated tumors.