Differential Regulation of Methylation-Regulating Enzymes by Senescent Stromal Cells Drives Colorectal Cancer Cell Response to DNA-Demethylating Epi-Drugs

Stem Cells International
Khushboo AgrawalMarián Hajdúch

Abstract

The advanced-stage colon cancer spreads from primary tumor site to distant organs where the colon-unassociated stromal population provides a favorable niche for the growth of tumor cells. The heterocellular interactions between colon cancer cells and colon-unassociated fibroblasts at distant metastatic sites are important, yet these cell-cell interactions for therapeutic strategies for metastatic colon cancer remain underestimated. Recent studies have shown the therapeutic potential of DNA-demethylating epi-drugs 5-azacytidine (AZA) and 5-aza-2'-deoxycytidine (DAC) for the treatment of solid tumors. While the effects of these epi-drugs alone or in combination with other anticancer therapies are well described, the influence of stromal cells and their secretome on cancer cell response to these agents remain elusive. In this study, we determined the effect of normal and senescent colon-unassociated fibroblasts and their conditioned medium on colorectal cancer (CRC) cell response to AZA and DAC using a cell-based DNA demethylation reporter system. Our data show that fibroblasts accelerate cell proliferation and differentially regulate the expression of DNA methylation-regulating enzymes, enhancing DAC-induced demethylation in CRC ...Continue Reading

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Citations

Apr 23, 2020·Frontiers in Oncology·Mengdi YangHui Zhao
Mar 7, 2021·Cancers·Teresa Gagliano, Claudio Brancolini
May 11, 2021·Frontiers in Oncology·Lila ZhuMengyuan Yang

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Methods Mentioned

BETA
X-Ray
Assay

Software Mentioned

[UNK] Image Analysis System
Columbus Image Analysis System
GraphPad
GraphPad Prism
ZEN Blue

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