Biomedicine Select

Angiogenesis (the recruitment and formation of new blood vessels) may be a limiting step in the growth of tumors. Recent work in animal models of human cancer suggests that even transient angiogenic signals can irreversibly block tumor dormancy, promoting tumor growth. Another report concludes that the production of an-giogenic factors may result from activation of a signaling pathway in the innate immune response. Other advances include the visualization of the tumor vasculature in living animals and the discovery of an antibody that has the potential to inhibit tumor angiogenesis by neutralizing a bioactive lipid. Malignant cells that migrate from the primary tumor site often remain as a micrometastasis in a dormant state. The recruitment of new blood vessels may contribute to the end of tumor dormancy, but the duration of the signal required for this so-called ''angiogenic switch'' is not known. Recent work by Indraccolo and colleagues (2006) suggests that only a brief exposure to angiogenic factors is needed to awaken dormant tumors. The authors first established a model of tumor dormancy by injecting MOLT-3 human leukemia cells into immunodeficient mice. In this model, a lack of expression of angiogenic factors by MOLT-3 cells prevents the formation of large tumors, although small poorly vascularized clusters of MOLT-3 cells were found at injection sites. However, large tumors did develop if MOLT-3 cells were coinjected with highly angiogenic Kaposi's sarcoma cells (KS-IMM) that had been irradiated to arrest their own proliferation. Both normal and irradiated KS-IMM cells expressed angiogenic factors, such as VEGF, bFGF, and IL-8. Flow cytometry showed that irradiated KS-IMM cells do not persist after four days, suggesting that their stimulating effect on tumor angiogenesis does not need to be sustained over long periods of time. The authors propose that even a short-lived alteration in the microenvironment of a dormant tumor, perhaps due to local inflammation , could lead to enhanced tumor angiogenesis and subsequent growth. In a related study, Naumov et al. (2006) separated angiogenic from nonangio-genic tumor cell populations by inoculating human breast adenocarcinoma, oste-osarcoma, and glioblastoma cells into immunodeficient mice. The model that Nau-mov et al. present for human tumor dormancy is unique because it takes advantage of the spontaneous switching of nonangiogenic tumor cells to an angio-genic phenotype. Angiogenic and nonangiogenic cells from each tumor type were compared for their ability to proliferate in vitro and for their tumorigenicity when re-injected into immunodeficient mice. Although both …