Remodelling of the bone marrow microenvironment by stromal hyaluronan modulates the malignancy of breast cancer cells.

Cell Communication and Signaling : CCS
Xiaoyan ChenFeng Gao

Abstract

Hyaluronan (HA) is an abundant component of the bone marrow (BM) extracellular matrix. Here, we investigated the abnormal deposition of HA in the BM microenvironment and its remodelling in mediating the malignancy of breast cancer cells (BCCs). BCCs were transplanted into nude mice by intracardiac injection. The BCCs were cocultured with BM-derived stromal HS5 cells. Then, the abnormal metabolism of HA and its correlation with the malignant growth and the intracellular signalling pathways of the BCCs were investigated. After knockdown/out of the HA receptor CD44 in cancer cells by shRNA and CRISPR/Cas9, the mechanism was investigated in vivo through intratibial inoculation and in vitro by coculture with HS5 cells. The malignancy of cancer cells was highly related to the degree of accumulation of HA in the BM. Further, stromal cell-derived HA, especially the mixed complex, significantly promoted the growth of BCCs and osteolysis by binding to the CD44 receptor. Additionally, the investigation of the underlying mechanism revealed that the PI3K, Cyclin D1, and CDK4 pathways were involved in the effect of bone stromal cell-derived HA on the BCC activities. These data suggested that HA in abnormal BM stroma might be a therapeutic ca...Continue Reading

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Methods Mentioned

BETA
flow cytometry
Protein Assay
ELISAs
PCR
transfection
electrophoresis
xenograft

Software Mentioned

Adobe Illustrator CC
GraphPad Prism

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