Expression profiles of angiogenesis in two high grade chondrosarcomas: A xenotransplant experience in nude mice

Abstract

Background. Chondrosarcomas (Chs) are malignant cartilage-forming tumors that represent the third most common malignant solid tumor of bone in adults. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to make a histological, immunohistochemical, ultrastructural and molecular characterization of the neovascularization established between xenotransplanted Chs and the host during the initial phases of growth in nude transfer, in order to find potential markers for distinguishing between high grades II and III Chs. Methods. two xenotransplanted high grade human Chs were evaluated. Tumor pieces were implanted subcutaneously on the backs of 14 athymic Balb-c nude mice. The animals were sacrificed 24, 48, and 96 hours; and 7, 14, 21 and 28 days after implantation. Two grade I Chs were also transferred in nude but did not grow. Results. Morphological differences were apparent between these two Chs during the early stages of neoplastic growth. Immunohistochemistry demonstrated overexpression of pro-angiogenic factors 24h-48h after tumor implantation. Additionally, neoplastic cells co-expressed chemokines (CXCL9, CXCL10 and GRO) and their receptors. Molecular studies showed two expression profiles, revealing an early and a late phase in the angiogenic process. Conclusion. High grade Chs demonstrated two different stages of induced angiogenesis, with an intimate association between structural and molecular events that might explain the different aggressive biological behavior of grade II and III Chs. The present model may be useful for testing the effect of anti-angiogenic drugs.