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Purpose <p>MMP11 exhibits significant overexpression in various cancers; however, its role in colorectal cancer (CRC) remains poorly understood. This study aimed to investigate the relationship between MMP11 and the prognosis of colorectal cancer and to evaluate the therapeutic potential of an MMP11 inhibitor.</p> Methods <p>Our study employed an integrative bioinformatics approach utilizing TIMER, GEPIA, UALCAN, and HPA datasets to comprehensively assess MMP11 expression patterns and their correlation with clinicopathological characteristics and tumor-infiltrating immune cells (TIICs) in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ). Overall survival (OS) data for CRC were extracted from the The Cancer Genome Atlas (TCGA). To investigate the therapeutic potential of MMP11 inhibition, we treated HCT116 and SW480 CRC cell lines with the MMP11 inhibitor RXP03. Colony formation and transwell assays were used to evaluated the proliferation and invasion abilities of CRC cells, while apoptosis was measured via TUNEL staining and flow cytometry. Additionally, xenograft tumor models were used to assess the tumor-suppressive effects of MMP11 inhibition.</p> Results <p>MMP11 expression was significantly upregulated in COAD and READ specimens compared to normal controls, and was correlated with age, tumor stage, histological subtype and nodal metastasis status. Kaplan-Meier survival analysis indicated that high MMP11 expression was an independent prognostic factor for poorer overall survival in CRC. TIMER analysis revealed that MMP11 transcription was strongly positively correlated with several TIICs, including CD4 + T cells, macrophages, and dendritic cells. Furthermore, MMP11 expression exhibited significant positive correlations with the infiltration levels of B7-H3 and TIM3 in CRC. <i>In vitro</i> experiments revealed that RXP03 significantly inhibited the proliferation and invasion of CRC cells and induced apoptosis. Xenograft experiments further demonstrated that RXP03 markedly suppressed the growth of colorectal tumors <i>in vivo.</i></p> Conclusion <p>MMP11 expression is associated with survival outcomes and levels of TIICs in CRC patients, suggesting its potential as a prognostic biomarker for CRC. Moreover, therapeutic intervention with the MMP11 inhibitor RXP03 demonstrates anti-tumor efficacy against CRC in both <i>in vitro</i> and <i>in vivo</i> models.</p>

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MMP11 predicts colorectal cancer outcomes and its inhibitor RXP03 exerts anti-tumor effects via apoptosis activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月7日

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  • Cheng Wang,
  • Peiyi Fu,
  • Jianping Sheng

摘要

Purpose

MMP11 exhibits significant overexpression in various cancers; however, its role in colorectal cancer (CRC) remains poorly understood. This study aimed to investigate the relationship between MMP11 and the prognosis of colorectal cancer and to evaluate the therapeutic potential of an MMP11 inhibitor.

Methods

Our study employed an integrative bioinformatics approach utilizing TIMER, GEPIA, UALCAN, and HPA datasets to comprehensively assess MMP11 expression patterns and their correlation with clinicopathological characteristics and tumor-infiltrating immune cells (TIICs) in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ). Overall survival (OS) data for CRC were extracted from the The Cancer Genome Atlas (TCGA). To investigate the therapeutic potential of MMP11 inhibition, we treated HCT116 and SW480 CRC cell lines with the MMP11 inhibitor RXP03. Colony formation and transwell assays were used to evaluated the proliferation and invasion abilities of CRC cells, while apoptosis was measured via TUNEL staining and flow cytometry. Additionally, xenograft tumor models were used to assess the tumor-suppressive effects of MMP11 inhibition.

Results

MMP11 expression was significantly upregulated in COAD and READ specimens compared to normal controls, and was correlated with age, tumor stage, histological subtype and nodal metastasis status. Kaplan-Meier survival analysis indicated that high MMP11 expression was an independent prognostic factor for poorer overall survival in CRC. TIMER analysis revealed that MMP11 transcription was strongly positively correlated with several TIICs, including CD4 + T cells, macrophages, and dendritic cells. Furthermore, MMP11 expression exhibited significant positive correlations with the infiltration levels of B7-H3 and TIM3 in CRC. In vitro experiments revealed that RXP03 significantly inhibited the proliferation and invasion of CRC cells and induced apoptosis. Xenograft experiments further demonstrated that RXP03 markedly suppressed the growth of colorectal tumors in vivo.

Conclusion

MMP11 expression is associated with survival outcomes and levels of TIICs in CRC patients, suggesting its potential as a prognostic biomarker for CRC. Moreover, therapeutic intervention with the MMP11 inhibitor RXP03 demonstrates anti-tumor efficacy against CRC in both in vitro and in vivo models.