3757 - Influence of eribulin on proliferation, migration and invasion properties of leiomyosarcoma cell line models

Background

Eribulin has an effect on proliferation, migration and invasion of sarcoma and breast cancer in vitro assays. A phase III clinical trial in patients with advanced liposarcoma (LPS) or leiomyosarcoma (LMS) showed an improvement in overall survival (OS) for the eribulin arm compared to dacarbazine, although no benefit was observed in the LMS restricted subgroup. Based on these results, eribulin was approved only for advanced LPS patients. The aim of the current study is to evaluate the effect of eribulin on key cell properties, like proliferation, migration, and invasion in LMS cell lines, in conventional 2D, but also 3D culture models.

Methods

Eribulin was kindly provided by Eisai Inc. (Andover, USA) and tested on CP0024 and SK-UT-1 human LMS cell lines. Cellular proliferation was determined by SRB assay on 2D, and measured by spheroid diameter and by propidium iodide and calcein-AM double staining in 3D cultures by Celigo Platform (Nexcelom, Lawrence, USA).Cells were treated with increased concentrations of eribulin to determine IC₅₀ values and its effect on proliferation. Chemotaxis and invasion were determined using transwell assay on 2D culture. Spheroids grown during 4 days were laid or embedded in matrigel for 3D assays and quantified over 3-7 additional days.

Results

Both cell lines had a mesenchymal-like appearance on monolayer culture, although SK-UT-1 had a more compact spheroid pattern compared to CP0024. Proliferation, migration, and invasion were examined after exposure to eribulin. The results showed that eribulin is active on both cell lines inhibiting proliferation in 2 and 3D culture conditions at concentrations below the nanomolar range. Moreover, eribulin significantly inhibited migration and invasion. To our knowledge, these findings are the first to demonstrate the effect of eribulin in LMS cell line 3D models.

Conclusions

Our results support the in vitro activity of eribulin in LMS cell lines and its further exploration as an agent with clinical benefit in patients with LMS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Eisai.

Disclosure

M. Mendiola: Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai. A. Gallego Martínez: Travel / Accommodation / Expenses, Non-remunerated activity/ies, training courses: Eisai. A. Redondo: Honoraria (self), Research grant / Funding (institution): Eisai. All other authors have declared no conflicts of interest.