Evidence map›Paper›PMID 42706676›Full record

ArticleIUBMB life2026

MMP9 Knockout by CRISPR-Cas9 Reduces Bladder Cancer Malignancy But Does Not Synergize With BCG and Anti-PD-L1 in an Orthotopic Mouse Model.

Juliana Alves de Camargo, Maria Carolina Lee, Milena Monteiro de Souza, Luana Pereira da Silva, Giovanna Vilas Boas Caetano, Karina Serafim da Silva, Carolina Mie Mioshi, Ruan Cesar Aparecido Pimenta, Patrícia Candido, Iran Amorim da Silva and 4 more

Erratum issuedAbstract read
In one paragraph

Article in IUBMB life, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Juliana Alves de CamargoLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0001-5624-3798
Maria Carolina LeeLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Milena Monteiro de SouzaLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Luana Pereira da SilvaLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Giovanna Vilas Boas CaetanoLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Karina Serafim da SilvaLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0003-4854-9302
Carolina Mie MioshiLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Ruan Cesar Aparecido PimentaPrecision Immunology Institute, Department of Immunology and Immunotherapy, and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID https://orcid.org/0000-0002-3423-5647
Patrícia CandidoLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0001-5887-5617
Iran Amorim da SilvaLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0001-5441-790X
Ericka Barbosa TrarbachLaboratory of Cellular and Molecular Endocrinology (LIM25), Endocrinology Department, Medicine School, University of São Paulo (FMUSP), São Paulo, Brazil.ORCID https://orcid.org/0000-0003-4570-2439
Katia Ramos Moreira LeiteLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0002-2615-7730
William Carlos NahasUro-Oncology Group, Urology Department, Institute of Cancer State of São Paulo (ICESP), São Paulo, Brazil.ORCID https://orcid.org/0000-0002-7395-8370
Sabrina Thalita Dos ReisLaboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0002-3564-3597

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundação de Amparo à Pesquisa do Estado de São Paulo 2022/02288-0Fundação de Amparo à Pesquisa do Estado de São Paulo 2022/08864-3
6 · The paper itself

Abstract

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.

Indexed as

B7-H1 AntigenBCG VaccineCRISPR-Cas SystemsImmune Checkpoint InhibitorsMatrix Metalloproteinase 9Urinary Bladder NeoplasmsAnimalsCell Line, TumorDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticHumansMiceMice, Inbred C57BLMice, KnockoutB7-H1 AntigenBCG VaccineCd274 protein, mouseImmune Checkpoint InhibitorsMatrix Metalloproteinase 9Mmp9 protein, mouseBCGbladder cancerCRISPR‐Cas9immunotherapyMMP9PD‐L1tumor microenvironment

Identifiers

PMID42706676
PMCPMC13550818

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.