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HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway.
Zhou, Siqi; Wang, Zhangding; Zhao, Dian; Fu, Yao; Zhang, Shu; Wang, Zhiping; Zou, Xiaoping.
Affiliation
  • Zhou S; Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China.
  • Wang Z; Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
  • Zhao D; Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
  • Fu Y; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang S; Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
  • Wang Z; Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China. zhangsgastro@nju.edu.cn.
  • Zou X; Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. zhangsgastro@nju.edu.cn.
World J Surg Oncol ; 22(1): 133, 2024 May 18.
Article in En | MEDLINE | ID: mdl-38762741
ABSTRACT

BACKGROUND:

Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated.

METHODS:

We initially conducted an analysis of the B7 family members' expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored.

RESULTS:

Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs).

CONCLUSION:

The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Cell Movement / Cell Proliferation / Proto-Oncogene Proteins c-akt / TOR Serine-Threonine Kinases / Epithelial-Mesenchymal Transition / ErbB Receptors Limits: Female / Humans / Male Language: En Journal: World J Surg Oncol Year: 2024 Document type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Cell Movement / Cell Proliferation / Proto-Oncogene Proteins c-akt / TOR Serine-Threonine Kinases / Epithelial-Mesenchymal Transition / ErbB Receptors Limits: Female / Humans / Male Language: En Journal: World J Surg Oncol Year: 2024 Document type: Article Affiliation country: China
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