Abstract P4-03-17: Tartrate-resistant acid phosphatase (TRACP) modulates breast cancer pre-metastatic niche

Abstract

Abstract Background: Tartrate-resistant acid phosphatase (TRACP or ACP5) is a metalloprotein enzyme that belongs to the acid phosphatase family and is mainly expressed by osteoclasts. It is a classic marker for bone resorption and osteoclast differentiation. TRACP expression is a useful serum marker for extensive bone metastasis. Recent studies have reported that TRACP promotes the invasion and distant metastasis of melanoma and breast cancer cells through the modulation of focal adhesion kinase (FAK) phosphorylation and epithelial cell migration. Therefore, TRACP has received considerable attention as a newly discovered proinvasion metastasis driver associated with different malignancies. Additionally, TRACP overexpression is indicative of the poor prognoses cancer patients and suggests that TRACP may have an important role in promoting tumor metastasis. Its detail mechanism in modulating cancer metastasis remains unknown. We have previously demonstrated the serum TRCAP 5a is a valuable marker in assessing disease activity, severity or systemic macrophage (inflammatory) burden. It has recently been found that up-regulation of TRACP promoted cancer cell invasion and lung metastasis, whereas TRACP knockdown inhibited these processes. Aims: No studies have previously addressed the question of extracellular effects of TRAP. The aim of this study was to evaluate if TRACP binds to and is endocytosed by cancer cells. We also aim to determine if extracellular TRACP affect oncogenesis or cancer progression, alter the cancer cell expressions of angiogenesis or adhesion molecules, or direct the treatment resistance or cancer prognosis. Results: Knockdown of TRACP significantly attenuated FoxM1-enhanced invasion and lung metastasis. Extracellular TRACP in culture media influenced the tumor invasion upon endocytosis. Significant increased invasion/migration was observed upon higher concentrations of TRACP. Tumor growth was significantly enhanced when the tumor xenografting previously primed with polarized M2Ø or TRACP protein, by enhanced metalloproteinase (MMP-9) and angiogenic factor (VEGF-A) expression Conclusions: TRACP or M2Ø-secreted TRACP could promote cancer growth and modulated the tissue and microenvironment and create pre-metastatic condition by cell adhesion/angiogenesis signaling alteration. TRACP-targeting strategy is plausible in breast cancer metastasis treatment. Citation Format: Dai M-S, Wu C-C, Chen L-C, Chen C-M, Chao T-Y. Tartrate-resistant acid phosphatase (TRACP) modulates breast cancer pre-metastatic niche [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-17.