In vitro study to evaluate the effect of granulocyte colony stimulating factor on colorectal adenocarcinoma and on mesenchymal stem cells trans differentiation into cancer stem cells by cancer cells derived exosomes

Abstract

Background

Colorectal cancer (CRC) is a common and lethal malignancies with poor prognosis. CRC cells release extracellular vesicles called exosomes to facilitate tumor progression by passing bioactive molecules such as proteins and nucleic acids between cells of the tumor and their microenvironment. Granulocyte colony stimulating factor (G-CSF) is a hematopoietic growth factor which mainly affects the lineage of neutrophil and exerts direct anti-tumor effects on various tumor types. The purpose of our study is to investigate the effect of G-CSF on CRC cells and to evaluate its capability to attenuate the potentiality of CRC cells derived exosomes to induce bone marrow-derived mesenchymal stem cells (BM-MSCs) malignant transformation into cancer stem cells (CSCs).

Results

The level of both lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1) (p = 0.014) & β-catenin (p = 0.01) was significantly decreased, whereas programmed cell death 4 (PDCD4) (p = 0.018) was increased in CRC exosomes pre-treated with G-CSF compared to untreated CRC exosomes. Additionally, there was a significant decrease in the cell proliferation in CRC cells pre-treated with G-CSF compared to untreated CRC cells (p = 0.008). Flow cytometric analysis of BM-MSCs showed that G-CSF could attenuate their transformation into CSCs.

Conclusion

G-CSF can be a promising therapeutic agent for CRC treatment.