Table 4.

Features of the tumor microenvironment that may affect cancer cell property and drug sensitivity

Research background	Description of tumor microenvironment	Microenvironment related effect	Ref.
New tissue culture model for research on colorectal cancer liver metastasis	Scaffolds from HC, CRC, HL, and CRLM were created by decellularization of the corresponding tissues. HT-29 and HCT116 cells were kept three-dimensionally in the scaffold	Epithelial-mesenchymal transition was observed in HT-29 cell culture in CRLM scaffold. Two CRC cell lines, HT-29 and HCT116, were 3D cultured in four different scaffolds (HC, CRC, HL, and CRLM)	D’Angelo et al.[48]
Extracellular vesicles	EVs containing various biomolecules were created. The EV-containing biomolecules could be transferred to other cells	The biomolecules transferred to recipient cells alter the cellular phenotypes of the recipient cells	Fontana et al.[49] Xavier et al.[50]
Exosome-mediated circular RNA transfer	Circ_000038 was transferred to recipient cells in an exosome-mediated fashion	The recipient cells became resistant to 5-fluorouracil by Circ_000038 with miR-217 and miR-485-3p	Zhao et al.[51]
A co-culture system of PBMCs and miR-146a-overexpressing HT-29 cells was created	miR-146a-overexpressing HT-29 cells and PBMC co-culture system led to increase in the population of regulatory T cell	Upregulated TNF-β and IL-10 in PBMCs and induction of irinotecan and 5-fluorouracil resistance were observed in miR-146a-overexpressing HT-29 cells	Khorrami et al.[52]

HC: Healthy colon; CRC: colorectal cancer; HL: healthy liver; CRLM: colorectal liver metastasis; EVs: extracellular vesicles; IL-10: interleukin-10; PBMCs: peripheral blood mononuclear cells; TNF-β: tumor necrosis factor-β.