Abstract 610: Effect of scaffold and growth factors on anti-cancer drug screening with multicellular spheroids: mimicking in vivo response

Abstract

Abstract Background: For in vitro cancer research, cancer microenvironment is being increasingly recognized as a key factor. In the past, several 3D cell culture models have been tested as the powerful method for reproducing cancer microenvironment. However, in some cases, the growth and drug sensitivity of cells grown on anchorage-independent 3D culture models have been different to that of cells grown in vivo. Further, development of the 3D culture model including the physical (the cell-ECM interaction (scaffold)) and chemical factor (cytokine) are essential for mimicking cancer microenvironment in vitro. Therefore, we explored the effect of the growth factor dependent proliferation and drug sensitivity in scaffold/scaffold-free culture models, and try to understand which method is mimicking in vivo response due to stimulation and suitable for anti-cancer drug development. Methods: We cultured lung cancer, breast cancer, pancreatic cancer and ovarian cancer cell line on monolayer, Matrigel (ECM-embedded 3D culture, scaffold type), NanoCuluture Plate (NCP, a gel-free scaffold type 3D culture plate) and Low adhesion round-bottom plate (scaffold-free 3D culture plate). For growth curve experiment upon addition of growth factors (EGF, HB-EGF, FGF, HRG), we evaluated cell viabilities by ATP assay in several cancer cell lines. We examined drug sensitivities of cancer cell lines against clinically active anti-cancer agents by addition of growth factors. Results: Growth factor promoted the proliferation of cancer cell lines cultured on NCP while it was not enhanced the cell growth when cultured on 2D, Matrigel and Low adhesion round-bottom plate. In drug response, the cells grown on NCP by growth factor stimulation was more sensitive to drug than 2D and other 3D culture models. Conclusion: Differences of the cell growth and drug sensitivity were appeared by effect of scaffold and growth factor. Growth factor dependent cell proliferation and drug sensitivity on NCP were similar to in vivo behavior (1). These results demonstrated that scaffold and growth factor are the novel approach to be mimicking the cancer microenvironment in vitro. Therefore, it is obvious that NCP can be used as a suitable 3D culture model for mimicking in vivo response and anti-cancer drug development. 1. J Cell Sci. 2009 Dec 1;122(Pt 23):4277-86. Citation Format: Norio Masuda, M. Mamunur Rahman, Kazuya Arai, Atsushi Mizuno, Manabu Itoh. Effect of scaffold and growth factors on anti-cancer drug screening with multicellular spheroids: mimicking in vivo response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 610.