IUBMB lifeSep 8, 2026

Removing MMP9 lowers bladder cancer severity but does not improve treatment with BCG and anti-PD-L1 in a mouse model

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 9, 2026

Abstract

Bladder cancer (BC) accounts for approximately 5% of new cancer cases worldwide.

MMP9 gene and protein expression were reduced in the MMP9-edited group compared to the control group.
Changes in gene expression included decreased ITGB3 and increased BAX in the MMP9-edited group.
The MMP9-edited group exhibited reduced migration and adhesion to the extracellular matrix.
No differences were observed in other matrix metalloproteinases (MMPs).
Animals in the control group experienced greater weight loss and lower survival rates compared to the treated groups.
MMP9 was associated with modulation of key cellular mechanisms but did not demonstrate synergistic effects with BCG and anti-PD-L1 therapy.

Simplified

Bladder cancer (BC) is the 10th most common cancer worldwide, accounting for approximately 5% of new cases. Several factors contribute to tumor progression, including increased MMP9. Recently, CRISPR-Cas9 and immunotherapy have offered high specificity for treatments; therefore, we edited MMP9 using CRISPR-Cas9 methodology to inhibit metastatic mechanisms and evaluated potential synergy with BCG and anti-PD-L1 therapy. We performed CRISPR-Cas9 gene editing using an RNP complex in the MB49 murine BC cell line. Gene expression of MMPs, integrins, and BAX was analyzed, along with protein expression. Cells were divided into a Scramble control group and CRISPR-Cas9 for the MMP9 edited group (MMP9-/-). Female C57BL/6 mice received orthotopic BC cells (scramble and MMP9-/- groups) treated with BCG and anti-PD-L1. Statistical analyses were performed using t test or ANOVA. MMP9 gene and protein expression were reduced in the MMP9-/- group compared with the scramble group. No differences were observed in other MMPs. Decreased ITGB3, increased BAX gene expression, as well as reduced migration and adhesion to ECM were observed in the MMP9-/- group. Animals in the scramble group showed greater weight loss and lower survival than treated groups. Overall, MMP9 modulated key cellular mechanisms, but did not show synergistic effects with BCG and anti-PD-L1 in vivo.

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Removing MMP9 lowers bladder cancer severity but does not improve treatment with BCG and anti-PD-L1 in a mouse model

Abstract

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