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CC BY 4.0 · Glob Med Genet 2023; 10(04): 348-356
DOI: 10.1055/s-0043-1777327
Original Article

Spleen-Derived CCL9 Recruits MDSC to Facilitate Tumor Growth in Orthotopic Hepatoma Mice

Baohua Li
1   General Surgery Department of Cadre's Ward, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
2   National & Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
3   Core Research Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
,
Wenjuan Li
4   Tumor Immunology Center of Precision Medical Research Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
,
Yingxue Liang
4   Tumor Immunology Center of Precision Medical Research Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
,
Chen Zhang
2   National & Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
,
Guangyao Kong
2   National & Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
,
Zongfang Li
1   General Surgery Department of Cadre's Ward, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
2   National & Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China
› Author Affiliations Funding/Acknowledgments This work was supported by the National Natural Science Foundation of China (81001309), the Natural Science Basic Research Program of Shaanxi Province of China (2023-JC-YB-643), and Science and Technology Program of Xi'an, Shaanxi Province of China (23YXYJ0178).
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Abstract

Objectives Spleen is involved in multiple diseases, the role of the spleen and spleen-derived factors in hepatocellular carcinoma (HCC) is still not clarified.

Methods In the current study, a murine H22 orthotopic hepatoma model was established. Three groups were divided: normal mice, tumor-bearing mice with spleen-preserving, and tumor-bearing mice with splenectomy. Spleen and tumor weights were recorded by weeks 1 and 2. The proportion of myeloid-derived suppressor cell (MDSC) in peripheral blood and tumor tissue was detected using flow cytometry. Protein chip assay was used to compare the differential cytokines between normal liver supernatant and tumor supernatant. The common upregulated cytokines both in spleen and tumor were focused and analyzed using gene expression profiling interactive analysis (GEPIA) database. Enzyme-linked immunosorbent assay was performed to verify the chip result, and to examine CCL9 expression before and after splenectomy. Spleen MDSC was sorted using flow cytometry, and chemotaxis assay was performed to demonstrate whether CCL9 attracted spleen MDSC.

Results The spleen enlarged during tumor progression, and compared with splenectomy group, there were faster tumor growth, shorter survival time, and higher proportions of MDSC in spleen-preserving group. Protein chip assay and GEPIA database revealed CCL9 was the most promising chemokine involved in HCC upregulated both in spleen and tumor tissue. CCL9 attracted MDSC in vitro, the level of CCL9 in tumor tissue was downregulated, and the percentage of MDSC was decreased after splenectomy.

Conclusion The results demonstrate that CCL9 may be derived from spleen; it facilitated HCC growth via the chemotaxis of MDSC, targeting CCL9 may be a promising strategy in HCC treatment.

Keywords

spleen - CCL9 - MDSC - hepatocellular carcinoma


Publication History

Article published online:
01 December 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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