Mesenchymal stem cells confer chemoresistance in breast cancer via a CD9 dependent mechanism


The cover for issue 37 of Oncotarget features Figure 7, "Flow diagram illustrating doxorubicin and 5FU chemoresistance in breast cancer tumors," by Ullah, et al.

In the present study, the scientists showed that when GFP labelled BMMSCs and RFP labelled HCC1806 cells are injected together in vivo, they create tumors which contain a new hybrid cell that has characteristics of both BMMSCs and HCC1806 cells.

Interestingly, when DP-HCC1806:BMMSCs were then injected into the mammary fat pad of NOD/SCID mice, they produced xenograft tumors which were smaller in size, and exhibited resistance to chemotherapy drugs, when compared tumors from HCC1806 cells alone.

Dr. Mujib Ullah from the Interventional Regenerative Medicine and Imaging Laboratory, Stanford University School of Medicine at the Department of Radiology in Palo Alto, CA 94304, USA said, "Breast cancer is the most diagnosed cancer and leading cause of cancer related death amongst women, with a global incidence of nearly 1.7 million new cases each year and over 520,000 deaths"

The progression of breast cancer and its subsequent development of chemoresistance, is highly dependent on the paracrine and cell-cell interactions between the tumor and its surrounding microenvironment, which consists of fibroblasts, immune cells, endothelial cells, and mesenchymal stem cells.

Figure 1: BMMSCs reduce tumor burden of HCC1806 xenografts in vivo.

MSCs are self-renewing multipotent cells found in bone marrow, adipose tissue, umbilical cord blood, and placental tissue, that are capable of differentiating into cells of the mesodermal lineage, such as adipocytes, chondrocytes, and osteocytes.

Indeed, the authors found that when BMMSCs and HCC1806 cells are co-cultured in vivo, they create tumors which contain a new hybrid cell that has characteristics of both BMMSCs and HCC1806 cells.

Following isolation of DP-HCC1806:BMMSCs, we then showed in vivo that this hybrid cell could create tumors like conventional HCC1806 cells, but that these tumors were reduced in size and exhibited increased resistance to chemotherapeutic agents.

The Ullah Research Team concluded, "Hence, to fully adopt BMMSCs for clinical applications it will be important for future studies to further define the cellular roles through which BMMSCs interact within a tumor microenvironment."

Full text - https://www.oncotarget.com/article/26952/text/

Correspondence to - Mujib Ullah - [email protected]

Keywords - MSCs, CD9, chemoresistance, cytokine, xenograft tumors

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