Expression of ANGIOPOIETIN-1, ANGIOPOIETIN-2, and TIE-2 in bone marrow and tumor during growth of experimental melanoma

Abstract

Abstract Adult vasculogenesis and angiogenesis are critical for tumor growth progression and metastasis. Variety of signaling molecules, such as angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and their tyrosine kinase receptor Tie-2 have been shown to play an important role in this process. Ang-1/Tie-2 signaling is involved in the maintenance of blood vessel integrity during vascular development. Binding of Ang-2 blocks Ang-1/Tie-2 signaling and thus may promote vascular remodeling. To study expression of these genes in the tumor and in non-tumor tissues we used a mouse model of subcutaneously growing melanoma B16. The tissue expression of Ang-1, Ang-2 and Tie-2 mRNAs was evaluated at different time-points of tumor growth by semiquantitative RT-PCR. The tumor overexpressed Ang-2, while Ang-1 was almost undetectable. In contrast bone marrow, spleen and liver showed comparable but low expression of Ang-1 and Ang-2. Ang-2 may be critically involved in tumor angiogenesis, however its pathogenetic role remains unclear. Moreover, we detected decreased Tie-2 expression in bone marrow during tumor progression. The metastasis of tumor cells into bone marrow were excluded by RT-PCR for melanoma specific tyrosinase gene. Our data suggest a systemic effect of the tumor on bone marrow Tie-2 expression.