2. Academic Validation
  3. PGD2 displays distinct effects in diffuse large B-cell lymphoma depending on different concentrations

PGD2 displays distinct effects in diffuse large B-cell lymphoma depending on different concentrations

  • Cell Death Discov. 2023 Feb 1;9(1):39. doi: 10.1038/s41420-023-01311-6.
Shunfeng Hu 1 2,  Tiange Lu 1,  Juanjuan Shang 1,  Yiqing Cai 1,  Mengfei Ding 1,  Xiangxiang Zhou 3 4 5,  Xin Wang 6 7 8 9
Affiliations

Affiliations

  • 1 Department of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
  • 2 Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
  • 3 Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China. xiangxiangzhou@sdu.edu.cn.
  • 4 Branch of National Clinical Research Center for Hematologic Diseases, Jinan, Shandong, 250021, China. xiangxiangzhou@sdu.edu.cn.
  • 5 National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, 251006, China. xiangxiangzhou@sdu.edu.cn.
  • 6 Department of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China. xinw007@126.com.
  • 7 Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China. xinw007@126.com.
  • 8 Branch of National Clinical Research Center for Hematologic Diseases, Jinan, Shandong, 250021, China. xinw007@126.com.
  • 9 National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, 251006, China. xinw007@126.com.
PMID: 36725845 DOI: 10.1038/s41420-023-01311-6
Abstract

Prostaglandin D2 (PGD2), an arachidonic acid metabolite, has been implicated in allergic responses, parasitic Infection and tumor development. The biological functions and molecular mechanisms of PGD2 in diffuse large B-cell lymphoma (DLBCL) are still undefined. In this study, we firstly found the high concentration of serum PGD2 and low expression of PGD2 receptor CRTH2 in DLBCL, which were associated with clinical features and prognosis of DLBCL patients. Interestingly, different concentration of PGD2 displayed divergent effects on DLBCL progression. Low-concentration PGD2 promoted cell growth through binding to CRTH2 while high-concentration PGD2 inhibited it via regulating cell proliferation, Apoptosis, cell cycle, and invasion. Besides, high-concentration PGD2 could induce ROS-mediated DNA damage and enhance the cytotoxicity of adriamycin, bendamustine and venetoclax. Furthermore, HDAC inhibitors, vorinostat (SAHA) and panobinostat (LBH589) regulated CRTH2 expression and PGD2 production, and CRTH2 inhibitor AZD1981 and high-concentration PGD2 enhanced their anti-tumor effects in DLBCL. Altogether, our findings demonstrated PGD2 and CRTH2 as novel prognostic biomarkers and therapeutic targets in DLBCL, and highlighted the potency of high-concentration PGD2 as a promising therapeutic strategy for DLBCL patients.

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