MTV/TM-011

Grem2-overexpressing Adipocytes Inhibit Proliferation and Invasion of Breast Cancer Cells

Gremlin-2 (GREM2), a bone morphogenetic protein antagonist, is known to inhibit adipogenesis but its role in cancer remains unclear. Unlike Gremlin-1, which promotes cancer, GREM2's function in tumor progression is not well understood. Jung et al. investigated whether GREM2's suppression of adipogenesis affects breast cancer cell growth and metastasis.

They used a 3D co-culture system to assess how GREM2-suppressed adipogenesis affects breast cancer cells. 3T3-L1-mock and 3T3-L1-Grem2 cells were differentiated into adipocytes for 9 days, then mixed with MTV/TM-011 breast cancer cells to form 3D spheroids (Fig. 1a). Fluorescent staining (red: cancer cells, green: adipocytes) confirmed even cell distribution. Spheroids with adipocytes-Grem2 were smaller (Fig. 1b) and showed reduced proliferation (Fig. 1c) compared to those with adipocytes-mock. Invasion assays (Fig. 1d) revealed that spheroids containing adipocytes-Grem2 had significantly smaller invasion areas on days 3, 7, and 9 (Fig. 1e, f). These findings indicate that Grem2-overexpressing adipocytes inhibit breast cancer cell proliferation and invasion.

Fig. 1. Adipocytes overexpressing Grem2 inhibit the proliferation and invasion of breast cancer cells (Jung J, Kim N H, et al., 2023).

GREM1 Contributes to the Proliferation, Migration, and Invasion of Breast Cancer Cells

The BMP antagonist Gremlin-1 (GREM1) is overexpressed in breast cancer and associated with metastasis, however the mechanism is not understood. Using in vitro assays and an orthotopic breast cancer mouse model Sung et al. examined the effect of knockdown and overexpression of GREM1 on breast cancer cell proliferation, migration and invasion. In order to validate the requirement for GREM1 in breast cancer cell growth and migration, they silenced GREM1 in MDA-MB-231 and MTV/TM-011 cells via lentiviral transduction (Fig. 2A). They found that knockdown of GREM1 significantly decreased cell proliferation (Fig. 2B) and migration as determined by wound healing assay (Fig. 2C–F). In contrast, transient overexpression of GREM1 (Fig. 3A) resulted in significantly increased proliferation (Fig. 3B), migration (Fig. 3C–F) and invasion (Fig. 3G and H) as compared to control. Taken together, their data indicates a role for GREM1 in breast cancer cell growth, migration and invasion.

Fig. 2. GREM1 knockdown inhibits the growth and mobility of breast cancer cells (Sung NJ, Kim NH, et al., 2020).

Fig. 3. GREM1 overexpression enhances the growth and mobility of breast cancer cells (Sung NJ, Kim NH, et al., 2020).