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The roles of P-selectin in cancer cachexia

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Abstract

P-selectin, a cell adhesion molecule of the selectin family, is expressed on the surface of activated endothelial cells (ECs) and platelets. Binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1) supports the leukocytes capture and rolling on stimulated ECs and increases the aggregation of leukocytes and activated platelets. Cancer cachexia is a systemic inflammation disorder characterized by metabolic disturbances, reduced body weight, loss of appetite, fat depletion, and progressive muscle atrophy. Cachexia status is associated with increased pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which activates ECs to release P-selectin. Single-nucleotide polymorphisms (SNPs) loci of P-selectin encoding gene SELP are associated with higher level of plasma P-selectin and increase the susceptibility to cachexia in cancer patients. Elevated P-selectin expression has been observed in the hypothalamus, liver, and gastrocnemius muscle in animal models with cancer cachexia. Increased P-selectin may cause excessive inflammatory processes, muscle atrophy, and blood hypercoagulation, thus facilitating the development of cancer cachexia. In this review, physiological functions of P-selectin and its potential roles in cancer cachexia have been summarized. We also discuss the therapeutic potential of P-selectin inhibitors for the treatment of cancer cachexia.

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Acknowledgements

We are grateful to the grants from National Nature Science Foundation of China (82171318 and 82241030), Shandong Taishan Scholarship (JuL), Academic Promotion Program of Shandong First Medical University (2019QL014), and Jinan City's Science and Technology Innovation Program of Clinical Medicine (202019175).

Funding

This study was supported by grants from National Nature Science Foundation of China (82171318 and 82241030), Shandong Taishan Scholarship (JuL), Academic Promotion Program of Shandong First Medical University (2019QL014) and Jinan City's Science and Technology Innovation Program of Clinical Medicine (202019175).

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Authors and Affiliations

  1. Department of Respiratory, Shandong Provincial Qianfoshan Hospital, School of Clinical Medicine, Weifang Medical College, Weifang, 261053, China

    Tingting Ling

  2. Institute of Microvascular Medicine, Medical Research Center, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Road, Jinan, 250014, China

    Jing Liu & Ju Liu

  3. Department of Respiratory, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China

    Liang Dong

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  1. Tingting Ling
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  4. Ju Liu
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All authors contributed to the article. This review was conceived and designed by LJ. The first draft of the manuscript was written by TL. LJ, JL and LD critically revised the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ju Liu.

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Ling, T., Liu, J., Dong, L. et al. The roles of P-selectin in cancer cachexia. Med Oncol 40, 338 (2023). https://doi.org/10.1007/s12032-023-02207-2

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