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JAML inhibits colorectal carcinogenesis by modulating the tumor immune microenvironment

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Abstract

It is necessary to explore new targets for the treatment of colon adenocarcinoma (COAD) according to the tumor microenvironment. The expression levels of JAML and CXADR were analyzed by bioinformatics analysis and validation of clinical samples. JAML over-expression CD8+ T cell line was constructed, and the proliferation activity was detected by MTT. The production of inflammatory factors was detected by ELISA. The expression of immune checkpoint PD-1 and TIM-3 was detected by Western blot. The apoptosis level was detected by flow cytometry and apoptosis markers. The AOM/DSS mouse model of colorectal cancer was constructed. The expression levels of JAML, CXADR and PD-1 were detected by PCR and Western blot, and the proportion of CD8+ T cells and exhausted T cells were detected by flow cytometry. The expression levels of JAML and CXADR were significantly decreased in colon cancer tissues. Overexpression of JAML can promote the proliferation of T cells, secrete a variety of inflammatory factors. Overexpression of CXADR can reduce the proliferation of colorectal cancer cells, promote apoptosis, and down-regulate the migration and invasion ability of tumor cells. Both JAML agonists and PD-L1 inhibitors can effectively treat colorectal cancer, and the combined use of JAML agonists and PD-L1 inhibitors can enhance the effect. JAML can promote the proliferation and toxicity of CD8+ T cells and down-regulate the expression of immune checkpoints in colon cancer. CXADR can inhibit the proliferation of cancer cells and promote the apoptosis. JAML agonist can effectively treat colorectal cancer by regulating CD8+ T cells.

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Data availability

Data to support the findings of this study is available on reasonable request from the corresponding author.

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Funding

This research work received supports from the Shandong Province Medical and Health Technology Development Plan Project (No. 202211000867), Outstanding Young Talents Project of Shandong Provincial Third Hospital (No. jqrc002) and Shandong Provincial Third Hospital Cultivation Fund Project (No. M2023002).

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Author notes

  1. Shiliang Cheng, Meng Li, Chunguang Li contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, 250031, Jinan, People’s Republic of China

    Shiliang Cheng, Meng Li, Yonggang Dai, Jinhua Zhuo, Jue Wang, Jingrong Qian & Zhihao Hao

  2. Emergency Medicine Department, Shandong Provincial Third Hospital, Shandong University, Jinan, People’s Republic of China

    Chunguang Li

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  1. Shiliang Cheng
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  2. Meng Li
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Correspondence to Shiliang Cheng.

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Supplementary Information

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Supplementary Figure 1

Bright-field and fluorescence images of control and JAML overexpression groups. Scale bars = 50 μm (PNG 180 kb)

High resolution image (TIF 1208 KB)

Supplementary Figure 2

The expression levels of 3 extracellular matrix glycoproteins. (A) The expression levels of fibronectin (FN1), laminin-1 (LAMB1) and tenascin-R (TNR) in normal and tumor tissues by TCGA database. (B) The expression levels of fibronectin (FN1), laminin-1 (LAMB1) and tenascin-R (TNR) were measured by western blot in CXADR-overexpressed and control HT29 cells (PNG 51.9 kb)

High resolution image (TIF 380 KB)

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Cheng, S., Li, M., Li, C. et al. JAML inhibits colorectal carcinogenesis by modulating the tumor immune microenvironment. In Vitro Cell.Dev.Biol.-Animal (2024). https://doi.org/10.1007/s11626-024-00881-8

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