Abstract

Cell biomechanics plays a major role as a promising biomarker for early cancer diagnosis and prognosis. In the present study, alterations in modulus of elasticity, cell membrane roughness, and migratory potential of MCF-7 (ER+) and SKBR-3 (HER2+) cancer cells were elucidated prior to and post treatment with conditioned medium from human umbilical mesenchymal stem cells (hUMSCs-CM) during static and dynamic cell culture. Moreover, the therapeutic potency of hUMSCs-CM on cancer cell’s viability, migratory potential, and F-actin quantified intensity was addressed in 2D surfaces and 3D scaffolds. Interestingly, alterations in ER+ cancer cells showed a positive effect of treatment upon limiting cell viability, motility, and potential for migration. Moreover, increased post treatment cell stiffness indicated rigid cancer cells with confined cell movement and cytoskeletal alterations with restricted lamellipodia formation, which enhanced these results. On the contrary, the cell viability and the migratory potential were not confined post treatment with hUMSCs-CM on HER2+ cells, possibly due to their intrinsic aggressiveness. The increased post treatment cell viability and the decreased cell stiffness indicated an increased potency for cell movement. Hence, the therapy had no efficacy on HER2+ cells.

Highlights

  • This study provides new insights and encourages the development of modalities for screening new therapeutic anti-cancer drugs regarding stem cell therapy

  • Concluding, we suggest that human umbilical mesenchymal stem cells (hUMSCs)-conditioned medium (CM) as a treatment can be satisfactorily applied in the case of ER+

  • The dynamic microenvironment of 3D ECM scaffolds and the bioreactor was satisfactorily applied to MCF-7 cancer cells, where the cell viability reduced markedly post treatment

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Summary

Introduction

Prognosis has improved due to advances in diagnostic and surgical techniques, breast cancer remains one of the most challenging diseases to treat [2]. The side effects of anti-cancer chemotherapy remain a major source of concern despite the improved efficacy and enhanced survival offered by modern treatments [3]. Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate the non-specific toxicity of anticancer drugs [4]. The short half-life of most chemotherapeutic drugs and the high systemic toxicity inhibits the effective delivery of anti-cancer drugs to the tumor [5]. Previous studies have shown that stem cells, and more precisely, human umbilical mesenchymal stem cells (hUMSCs), can attenuate tumor growth of triple-negative cancer and bronchioloalveolar carcinoma [7,8]

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