2. Academic Validation
  3. Dual roles of HK3 in regulating the network between tumor cells and tumor-associated macrophages in neuroblastoma

Dual roles of HK3 in regulating the network between tumor cells and tumor-associated macrophages in neuroblastoma

  • Cancer Immunol Immunother. 2024 May 7;73(7):122. doi: 10.1007/s00262-024-03702-9.
Xin Wu 1 2,  Tao Mi 1 2,  Liming Jin 1 2,  Chunnian Ren 1 2,  Jinkui Wang 1 2,  Zhaoxia Zhang 1 2,  Jiayan Liu 1 2,  Zhaoyin Wang 1 2,  Peng Guo 1 2 3,  Dawei He 4 5
Affiliations

Affiliations

  • 1 Department of Urology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.
  • 2 Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China.
  • 3 Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
  • 4 Department of Urology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China. hedawei@hospital.cqmu.edu.cn.
  • 5 Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China. hedawei@hospital.cqmu.edu.cn.
PMID: 38714539 DOI: 10.1007/s00262-024-03702-9
Abstract

Neuroblastoma (NB) is the most common and deadliest extracranial solid tumor in children. Targeting tumor-associated macrophages (TAMs) is a strategy for attenuating tumor-promoting states. The crosstalk between Cancer cells and TAMs plays a pivotal role in mediating tumor progression in NB. The overexpression of Hexokinase-3 (HK3), a pivotal Enzyme in glucose metabolism, has been associated with poor prognosis in NB patients. Furthermore, it correlates with the infiltration of M2-like macrophages within NB tumors, indicating its significant involvement in tumor progression. Therefore, HK3 not only directly regulates the malignant biological behaviors of tumor cells, such as proliferation, migration, and invasion, but also recruits and polarizes M2-like macrophages through the PI3K/AKT-CXCL14 axis in neuroblastoma. The secretion of lactate and histone lactylation alterations within tumor cells accompanies this interaction. Additionally, elevated expression of HK3 in M2-TAMs was found at the same time. Modulating HK3 within M2-TAMs alters the biological behavior of tumor cells, as demonstrated by our in vitro studies. This study highlights the pivotal role of HK3 in the progression of NB malignancy and its intricate regulatory network with M2-TAMs. It establishes HK3 as a promising dual-functional biomarker and therapeutic target in combating neuroblastoma.

Keywords

HK3; M2-like macrophages; Neuroblastoma; Pediatric solid tumor; TAMs; TME.

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