Specific tumor-stroma interactions of EBV-positive Burkitt's lymphoma cells in the chick chorioallantoic membrane

All cell-lines formed solid tumors. However, we observed strong differences in the behavior of EBV+ and EBV- cell-lines. Tumor borders of EBV+ cells were very fuzzy and numerous cells migrated into the CAM. In EBV- tumors, the borders were much better defined. In contrast to EBV- cells, the EBV+ cells induced massive immigration of chick leukocytes at the tumor borders and the development of granulation tissue with large numbers of blood vessels and lymphatics, although the expression of pro- and anti-angiogenic forms of Vascular Endothelial Growth Factors/receptors was the same in all BL cell-lines tested. The EBV+ cell-lines massively disseminated via the lymphatics and completely occluded them.Our data suggest that the EBV+ cells attract pro-angiogenic leukocytes, which then induce secondary tumor-stroma interactions contributing to the progression of BL. We show that the CAM is a highly suitable in vivo model to study the differential behavior of BL cell-lines.With conventional chemotherapy, long-term remission can be achieved in approximately 60% of patients with disseminated "aggressive" Non-Hodgkin lymphoma (NHL) [1]. The disease incidence is increasing, but etiologic factors contributing to this phenomenon remain still largely unknown. Although it is a curable disease, many patients do not achieve complete remission, or they relapse after conventional chemotherapy. Tumor- and host-related parameters are likely to reflect some underlying biologic mechanisms and differences in the response to therapy [2,3]. One suggestion is that deregulated components of the immune system may be linked to the incidence and clinical course of lymphomas, and the development of acute or chronic inflammatory reactions at the tumor site. Cytokines, as major mediators of inflammation, were found to be associated with the transformation of lymphatic malignancies either as autocrine growth factors for the transformed cells or as factors rebuilding the tumor microenvironment, likely a