PLXNB1/SEMA4D signals mediate interactions between malignant epithelial and immune cells to promote colorectal cancer liver metastasis

Zixue Xuan ^1,2, Yuan Zhang ², Dan Li ²

⁰Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Zhejiang, Hangzhou, China.

Journal of Cellular and Molecular Medicine +

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October 23, 2024

View abstract on PubMed

Summary

Colorectal cancer liver metastases involve specific epithelial cell subtypes (Epi-11) interacting with immune cells. This crosstalk, mediated by the PLXNB1/SEMA4D axis, impacts patient prognosis and cancer cell behavior.

Area Of Science

Oncology
Immunology
Genomics

Background

Colorectal cancer (CRC) liver metastases (LM) arise from complex interactions between tumor cells and their microenvironment.
Understanding cellular heterogeneity in primary CRC and LM is crucial for identifying drivers of metastasis.

Purpose Of The Study

To characterize cellular heterogeneity in CRC and LM using single-cell sequencing.
To identify intercellular communication pathways between epithelial and immune cells in CRC and LM.
To develop a prognostic model based on metastatic epithelial cell gene expression.

Main Methods

Integrated single-cell sequencing data analysis.
Construction of a prognostic model using gene expression data.
Multiplex immunofluorescence staining.
In vitro assays (wound healing, migration, apoptosis).

Main Results

Identified approximately 17 epithelial cell subtypes, with Epi-11 cells highly expressed in LM.
High expression of the Epi-11 metastasis-related genetic profile correlated with poorer prognosis.
Epi-11 cells showed increased interaction with myeloid and T/NK cells in LM via the PLXNB1/SEMA4D axis.
High SEMA4D expression correlated with decreased overall survival in CRC patients.
SEMA4D knockdown inhibited cell migration and promoted apoptosis in vitro.

Conclusions

Epi-11 cells represent a key epithelial subset driving CRC liver metastasis.
The PLXNB1/SEMA4D signaling axis mediates crosstalk between Epi-11 cells and immune cells.
Targeting this axis may offer therapeutic strategies for colorectal cancer liver metastasis.

Keywords:

PLXNB1/SEMA4D colorectal cancer liver metastasis single‐cell sequencing tumour microenvironment

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