Abstract P2-01-07: M2-like tumor-associated macrophages require Tartrate-resistant acid phosphatase as overall function to promote breast cancer metastasis

Abstract

Tartrate-resistant acid phosphatase (TRAP) is a member of the purple acid phosphatase family and is also known as type 5 acid phosphatase. It is mainly expressed in cells of the monocyte lineage, including osteoclasts, macrophages, and dendritic cells (DCs). There are two isoforms of TRAP enzyme: TRAP-5a and TRAP5b, and TRAP-5b is produced by post-translational modification of TRAP-5a. TRAP-5b is the major isoform of TRAP secreted by osteoclasts and it has been shown that TRAP-5b activity correlates with the number of osteoclasts and serum activity in rat and human studies. In contrast, macrophages and DCs are thought to secrete TRAP-5a as the major subtype, whereas TRAP-5a is a non-specific marker of macrophage activation. The recent studies show that higher-grade proliferative tumors with much necrosis were associated with abundant macrophage expressing TRAP. Here we generate TRAP-/- knockout mice to study the function of TRAP in tumorigenesis. In vitro experiments have found that the expression of TRAP in macrophages is essential for the full promoting tumor function of M2-like tumor-associated macrophages (TAM) including tumor growth and metastasis. Marrow-derived macrophages (BMDM) extracted from the TRAP-/- mice lost promote tumor migration activity. The 4T1 tumor (murine breast cancer cell line) conditioned medium was used to induce TAM formation found M2-like TAM formation in wild type BMDM was promoted higher than that of TRAP-/- BMDM. In contrast, the TRAP-/- is much higher M1-like TAM formation than the wild type. Xenograft tumor formation assays were used to monitor tumor formation by combining 4T1 and different M2 polarized macrophages into BALB/c mice. M2-polarized macrophages with trap-defective BMDM showed reduced promoted neoplastic activity compared to wild type. In MMTV-PyMT transgenic mice, spontaneous tumor formation in knockout trap-/- significantly repressed tumor formation compared to TRAP+/+ wild type mice. Finally, we hypothesized that TRAP is essential for the full function of M2-like tumor-associated macrophages and promotes tumor metastasis. Citation Format: Dai M-S, Lo H-C, Chen L-C, Janckilla A, Tseng S-F. M2-like tumor-associated macrophages require Tartrate-resistant acid phosphatase as overall function to promote breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-07.