Microenvironment Promotes Tumor Cell Reprogramming in Human Breast Cancer Cell Lines

Abstract

The microenvironment drives mammary gland development and function, and may influence significantly both malignant behavior and cell growth of mammary cancer cells. By restoring context, and forcing cells to properly interpret native signals from the microenvironment, the cancer cell aberrant behavior can be quelled, and organization re-established. In order to restore functional and morphological differentiation, human mammary MCF-7 and MDA-MB-231 cancer cells were allowed to grow in a culture medium filled with a 10% of the albumen (EW, Egg White) from unfertilized chicken egg. That unique microenvironment behaves akin a 3D culture and induces MCF-7 cells to produce acini and branching duct-like structures, distinctive of mammary gland differentiation. EW-treated MDA-MB-231 cells developed buds of acini and duct-like structures. Both MCF-7 and MDA-MB-231 cells produced β-casein, a key milk component. Furthermore, E-cadherin expression was reactivated in MDA-MB-231 cells, as a consequence of the increased cdh1 expression; meanwhile β-catenin – a key cytoskeleton component – was displaced behind the inner cell membrane. Such modification hinders the epithelial-mesenchymal transition in MDA-MB-231 cells. This differentiating pathway is supported by the contemporary down-regulation of canonical pluripotency markers (Klf4, Nanog). Given that egg-conditioned medium behaves as a 3D-medium, it is likely that cancer phenotype reversion could be ascribed to the changed interactions between cells and their microenvironment.

The Role of Krüppel-like Factor 4 in Renal Fibrosis

“…Because KLF4 is expressed in kidney cells (Hayashi et al, 2014 ), the ability to reprogramming somatic cells into IPS cells makes it possible to utilize KLF4 as a novel therapeutic target for Chronic kidney disease (CKD; D'Anselmi et al, 2013 ; Yamaguchi et al, 2014 ). Moreover, epigenetic modifications are known to play an essential role in kidney function and development (Dressler, 2008 ), and overexpression of KLF4 can reduce DNA methylation at the nephrin promoter, increasing the expression of nephrin and reducing the expression of mesenchymal genes (Hayashi et al, 2014 ).…”

“…KLF4 thus regulates numerous cellular processes, including proliferation, differentiation, apoptosis, migration, and invasion (Wang et al, 2015 ). Furthermore, KLF4 plays a specific role in cell reprogramming and differentiation, transforming somatic cells into induced pluripotent stem cells (IPS; D'Anselmi et al, 2013 ; Yamaguchi et al, 2014 ).…”

SMT and TOFT: Why and How They are Opposite and Incompatible Paradigms

“…By placing cancer cells into ''normal'' microenvironments-i.e., by restoring a normal, strong morphogenetic field-the tumor phenotype can be reverted into a normal one. Cancer cells exposed to embryonic morphogenetic fields D'Anselmi et al 2013;Pierce and Wallace 1971), or cultured in 3D-reconstructed biological microenvironments mimicking the normal tissue architecture (Willhauck et al 2007;Maffini et al 2004) undergo apoptosis and differentiation, eventually ending in the reprogramming of a ''normal'' phenotype (Mintz and Illmensee 1975;Hendrix et al 2007;Kenny and Bissell 2003).…”

Epigenetics changes caused by the fusion of human embryonic stem cell and ovarian cancer cells

“…Targeted therapy has been a hotspot for tumour treatment [ 13 , 14 ], which changes the site-directed genetic characteristics of cancer cells according to the therapeutic goal to treat the diseases [ 15 – 17 ]. The most important method for reconstruction of tumour cell specificity is reprogramming [ 18 – 20 ]. At present co-culture of stem cell extracts and cell fusion are the most common reprogramming methods [ 21 – 25 ].…”