LTBP-2 confers pleiotropic suppression and promotes dormancy in a growth factor permissive microenvironment in nasopharyngeal carcinoma

This study identified LTBP-2 as a pleiotropic tumor suppressor in nasopharyngeal carcinoma, which safeguards against critical malignant behaviors of tumor cells. LTBP-2 expression was significantly decreased or lost in up to 100% of NPC cell lines (7/7) and 80% of biopsies (24/30). Promoter hypermethylation was found to be involved in LTBP-2 silencing. Using a tetracycline-regulated inducible expression system, we unveiled functional roles of LTBP-2 in suppressing colony formation, anchorage-independent growth, cell migration, angiogenesis, VEGF secretion, and tumorigenicity. Three-dimensional culture studies suggested the involvement of LTBP-2 in maintenance of tumor cell dormancy in a growth factor favorable microenvironment.

► LTBP-2 was significantly down-regulated in NPC cell lines and biopsies. ► LTBP-2 silencing is associated with promoter hypermethylation. ► LTBP-2 suppresses malignancy by impairing in vitro & in vivo cell growth properties. ► LTBP-2 pleiotropically inhibits angiogenesis, VEGF secretion and migration. ► LTBP-2 confers tumor cell dormancy in microenvironment favorable for metastasis.