Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer.

ABSTRACT:

Background

MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth.

Methods

Murine bone marrow-derived MSCs were characterized by their surface markers and differentiation abilities. Proliferation and migration assays were performed in order to evaluate the functions of MSCs on cancer cells. CCL2 expression in MSCs was reduced by small interfering RNA (siRNA) or completely disrupted by CRISPR/Cas9 knockout (KO) approaches. An immune-competent syngeneic murine model of prostate cancer was applied in order to assess the role of tumor cell- and MSC-derived CCL2. The tumor microenvironment was analyzed to monitor the immune profile.

Results

We confirmed that tumor cell-derived CCL2 was crucial for tumor growth and MSCs migration. CCL2 KO MSCs inhibited the migration of the monocyte/macrophage but not the proliferation of tumor cells in vitro. However, the mice co-injected with tumor cells and CCL2 KO MSCs exhibited anti-tumor effects when compared with those given tumor cell alone and with control MSCs, partly due to increased infiltration of CD45⁺CD11b⁺Ly6G^- mononuclear myeloid cells.

Conclusions

Disruption of MSC-derived CCL2 enhances anti-tumor functions in an immune-competent syngeneic mouse model for prostate cancer.

SUBMITTER: Bui QT 

PROVIDER: S-EPMC9857005 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature