Abstract 1439: RANK expression by osteosarcoma cells increases lung metastasis in Nude mouse while has no effect in immune-competent mouse

Abstract

Background: Osteosarcoma, the most frequent malignant primary bone tumor, is characterized by an osteoid tumor tissue formation associated to a tumor-induced osteolysis. Lung metastasis occurs in some osteosarcomas with dramatic consequence for patient lifespan. Expression of RANK has been reported in some osteosarcoma cells and the question of the potential repercussion on tumor growth, tumor-induced osteolysis and lung metastasis was raised. Methods: Human HOS, human MG63 and mouse MOS-J osteosarcoma cell-lines were transfected to stably over-express RANK and injected in para-tibia muscle of Nude mice and syngeneic C57BL/6 mice for MOS-J cells. Tumor growth was follow and associated osteolysis analyzed by micro-CT and histology comparatively to injections of native cells. Lung metastases were numbered in each group. Results: In Nude mouse RANK over-expression, whatever the cell-line considered (human or mouse), induces a significant increase of the number of lung metastasis while the tumor growth and the induced osteolysis are not affected. Injections of a RANKL blocking antibody reverse the impact of RANK over-expression on lung metastasis. In the C57BL/6, RANK over-expression has no impact on the lung metastasis and tumor-induced osteolysis. The tumor growth was slightly reduced. Conclusions: Reported data evidence that RANK expression by osteosarcoma cells has no significant effect on the tumor growth and tumor-induced osteolysis but in immune-deficient Nude mouse induces an important increase of the lung metastases dependently of RANKL stimulation. Citation Format: Benjamin Navet, Kosei Ando, Hideo Yagita, Christopher G. Mueller, Dominique Heymann, Frederic Lezot. RANK expression by osteosarcoma cells increases lung metastasis in Nude mouse while has no effect in immune-competent mouse. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1439. doi:10.1158/1538-7445.AM2015-1439