دورية أكاديمية
Small-molecule inhibitor HI-TOPK-032 improves NK-92MI cell infiltration into ovarian tumours.
| العنوان: | Small-molecule inhibitor HI-TOPK-032 improves NK-92MI cell infiltration into ovarian tumours. |
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| المؤلفون: | Deng M; Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China., Yang R; Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China., Sun Q; Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China., Zhang J; Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China., Miao J; Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China. |
| المصدر: | Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2024 May; Vol. 134 (5), pp. 629-642. Date of Electronic Publication: 2024 Mar 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Country of Publication: England NLM ID: 101208422 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-7843 (Electronic) Linking ISSN: 17427835 NLM ISO Abbreviation: Basic Clin Pharmacol Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2005-> : Oxford : Blackwell Original Publication: Copenhagen, Denmark : Oxford, UK : Nordic Pharmacological Society Distributed by Blackwell Munksgaard, 2004- |
| مواضيع طبية MeSH: | Interleukin-2* , Ovarian Neoplasms*/drug therapy , Indolizines* , Quinoxalines*, Humans ; Mice ; Animals ; Female ; Apoptosis ; Cell Line, Tumor ; Extracellular Signal-Regulated MAP Kinases ; Killer Cells, Natural |
| مستخلص: | The effectiveness of natural killer (NK) cells transferred adoptively in combating solid tumours is limited by challenges such as their difficulty in penetrating tumours from the bloodstream and maintaining viability without the support of interleukin-2 (IL-2). Genetically modified NK-92MI cells, which can release IL-2 to sustain their viability, have been identified as a promising alternative. This adaptation addresses the negative consequences of systemic IL-2 administration. The role of PSD-95/discs large/ZO-1 (PDZ)-binding kinase (PBK) in cancer development is recognized, but its effects on immunity are not fully understood. This study explores how PBK expression influences the ability of NK-92MI cells to infiltrate ovarian tumours. Elevated levels of PBK expression have been found in various cancers, including ovarian cancer (OV), with analyses showing higher PBK mRNA levels in tumour tissues compared to normal ones. Immunohistochemistry has confirmed increased PBK expression in OV tissues. Investigations into PBK's role in immune regulation reveal its association with immune cell infiltration, indicating a potentially compromised immune environment in OV with high PBK expression. The small-molecule inhibitor HI-TOPK-032, which inhibits PBK, enhances the cytotoxicity of NK-92MI cells toward OV cells. It increases the production of interferon-γ and tumour necrosis factor-α, reduces apoptosis and encourages cell proliferation. Mechanistic studies showed that contact with OV cells treated with HI-TOPK-032 upregulates CD107a on NK-92 cells. In vivo studies demonstrated that HI-TOPK-032 improves the antitumour effects of NK-92MI cells in OVCAR3 Luc xenografts, extending survival without significant side effects. Safety assessments in mice confirm HI-TOPK-032's favourable safety profile, highlighting its potential as a viable antitumour therapy. These results suggest that combining NK-92MI cells with HI-TOPK-032 enhances antitumour effectiveness against OV, indicating a promising, safe and effective treatment strategy that warrants further clinical investigation. (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.) |
| References: | Bast RC Jr, Matulonis UA, Sood AK, et al. Critical questions in ovarian cancer research and treatment: report of an American Association for Cancer Research Special Conference. Cancer. 2019;125(12):1963‐1972. doi:10.1002/cncr.32004. Mirza MR, Coleman RL, González‐Martín A, et al. The forefront of ovarian cancer therapy: update on PARP inhibitors. Ann Oncol. 2020;31(9):1148‐1159. doi:10.1016/j.annonc.2020.06.004. Pujade‐Lauraine E, Fujiwara K, Ledermann JA, et al. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum‐resistant or platinum‐refractory ovarian cancer (JAVELIN Ovarian 200): an open‐label, three‐arm, randomised, phase 3 study. Lancet Oncol. 2021;22(7):1034‐1046. doi:10.1016/S1470‐2045(21)00216‐3. Deng M, Tang F, Chang X, et al. Immunotherapy for ovarian cancer: disappointing or promising? Mol Pharm. 2024;21(2):454‐466. doi:10.1021/acs.molpharmaceut.3c00986. Zöller T, Wittenbrink M, Hoffmeister M, Steinle A. Cutting an NKG2D ligand short: cellular processing of the peculiar human NKG2D ligand ULBP4. Front Immunol. 2018;9:620. doi:10.3389/fimmu.2018.00620. Ishigami S, Natsugoe S, Tokuda K, et al. Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer. 2000;88(3):577‐583. doi:10.1002/(SICI)1097‐0142(20000201)88:3<577::AID‐CNCR13>3.0.CO;2‐V. Murray S, Lundqvist A. Targeting the tumor microenvironment to improve natural killer cell‐based immunotherapies: on being in the right place at the right time, with resilience. Hum Vaccin Immunother. 2016;12(3):607‐611. doi:10.1080/21645515.2015.1096458. Gras Navarro A, Björklund AT, Chekenya M. Therapeutic potential and challenges of natural killer cells in treatment of solid tumors. Front Immunol. 2015;6:202. doi:10.3389/fimmu.2015.00202. Aksamitiene E, Kholodenko BN, Kolch W, Hoek JB, Kiyatkin A. PI3K/Akt‐sensitive MEK‐independent compensatory circuit of ERK activation in ER‐positive PI3K‐mutant T47D breast cancer cells. Cell Signal. 2010;22(9):1369‐1378. doi:10.1016/j.cellsig.2010.05.006. Roh E, Lee MH, Zykova TA, et al. Targeting PRPK and TOPK for skin cancer prevention and therapy. Oncogene. 2018;37(42):5633‐5647. doi:10.1038/s41388‐018‐0350‐9. Herbert KJ, Ashton TM, Prevo R, Pirovano G, Higgins GS. T‐LAK cell‐originated protein kinase (TOPK): an emerging target for cancer‐specific therapeutics. Cell Death Dis. 2018;9(11):1089. doi:10.1038/s41419‐018‐1131‐7. Chang CF, Chen SL, Sung WW, et al. PBK/TOPK expression predicts prognosis in oral cancer. Int J Mol Sci. 2016;17(7):1007. doi:10.3390/ijms17071007. Lee YJ, Park JH, Oh SM. TOPK promotes epithelial‐mesenchymal transition and invasion of breast cancer cells through upregulation of TBX3 in TGF‐β1/Smad signaling. Biochem Biophys Res Commun. 2020;522(1):270‐277. doi:10.1016/j.bbrc.2019.11.104. Hayashi T, Hayakawa Y, Koh M, et al. Impact of a novel biomarker, T‐LAK cell‐originating protein kinase (TOPK) expression on outcome in malignant glioma. Neuropathology. 2018;38(2):144‐153. doi:10.1111/neup.12446. Kim DJ, Li Y, Reddy K, et al. Novel TOPK inhibitor HI‐TOPK‐032 effectively suppresses colon cancer growth. Cancer Res. 2012;72(12):3060‐3068. doi:10.1158/0008‐5472.CAN‐11‐3851. Joel M, Mughal AA, Grieg Z, et al. Targeting PBK/TOPK decreases growth and survival of glioma initiating cells in vitro and attenuates tumor growth in vivo. Mol Cancer. 2015;14(1):121. doi:10.1186/s12943‐015‐0398‐x. Ikeda Y, Park JH, Miyamoto T, et al. T‐LAK cell‐originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in ovarian cancer. Clin Cancer Res. 2016;22(24):6110‐6117. doi:10.1158/1078‐0432.CCR‐16‐0207. Stefka AT, Johnson D, Rosebeck S, Park JH, Nakamura Y, Jakubowiak AJ. Potent anti‐myeloma activity of the TOPK inhibitor OTS514 in pre‐clinical models. Cancer Med. 2020;9(1):324‐334. doi:10.1002/cam4.2695. Ma H, Han F, Yan X, et al. PBK promotes aggressive phenotypes of cervical cancer through ERK/c‐Myc signaling pathway. J Cell Physiol. 2021;236(4):2767‐2781. doi:10.1002/jcp.30134. Tveden‐Nyborg P, Bergmann TK, Jessen N, Simonsen U, Lykkesfeldt J. BCPT 2023 policy for experimental and clinical studies. Basic Clin Pharmacol Toxicol. 2023;133(4):391‐396. doi:10.1111/bcpt.13944. Deng M, Wu D, Zhang Y, Jin Z, Miao J. MiR‐29c downregulates tumor‐expressed B7‐H3 to mediate the antitumor NK‐cell functions in ovarian cancer. Gynecol Oncol. 2021;162(1):190‐199. doi:10.1016/j.ygyno.2021.04.013. Sampath P, Li J, Hou W, Chen H, Bartlett DL, Thorne SH. Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects. Mol Ther. 2013;21(3):620‐628. doi:10.1038/mt.2012.257. Xu W, Yang W, Wu C, Ma X, Li H, Zheng J. Enolase 1 correlated with cancer progression and immune‐infiltrating in multiple cancer types: a pan‐cancer analysis. Front Oncol. 2021;10:593706. doi:10.3389/fonc.2020.593706. Leffers N, Fehrmann RS, Gooden MJ, et al. Identification of genes and pathways associated with cytotoxic T lymphocyte infiltration of serous ovarian cancer. Br J Cancer. 2010;103(5):685‐692. doi:10.1038/sj.bjc.6605820. Wu SY, Lin KC, Lawal B, Wu ATH, Wu CZ. MXD3 as an onco‐immunological biomarker encompassing the tumor microenvironment, disease staging, prognoses, and therapeutic responses in multiple cancer types. Comput Struct Biotechnol J. 2021;19:4970‐4983. doi:10.1016/j.csbj.2021.08.047. Bing SJ, Justesen S, Wu WW, et al. Differential T cell immune responses to deamidated adeno‐associated virus vector. Mol Ther Methods Clin Dev. 2022;24:255‐267. doi:10.1016/j.omtm.2022.01.005. Meza Guzman LG, Keating N, Nicholson SE. Natural killer cells: tumor surveillance and signaling. Cancers (Basel). 2020;12(4):952. doi:10.3390/cancers12040952. Xu Z, Zeng S, Gong Z, Yan Y. Exosome‐based immunotherapy: a promising approach for cancer treatment. Mol Cancer. 2020;19(1):160. doi:10.1186/s12943‐020‐01278‐3. Lee EHC, Wong DCP, Ding JL. NK cells in a tug‐of‐war with cancer: the roles of transcription factors and cytoskeleton. Front Immunol. 2021;12:734551. doi:10.3389/fimmu.2021.734551. Davis ZB, Felices M, Verneris MR, Miller JS. Natural killer cell adoptive transfer therapy: exploiting the first line of defense against cancer. Cancer J. 2015;21(6):486‐491. doi:10.1097/PPO.0000000000000156. Kilbourn RG, Fonseca GA, Trissel LA, Griffith OW. Strategies to reduce side effects of interleukin‐2: evaluation of the antihypotensive agent NG‐monomethyl‐L‐arginine. Cancer J Sci Am. 2000;6(Suppl 1):S21‐S30. Donohue JH, Rosenberg SA. The fate of interleukin‐2 after in vivo administration. J Immunol. 1983;130(5):2203‐2208. doi:10.4049/jimmunol.130.5.2203. Wennerberg E, Kremer V, Childs R, Lundqvist A. CXCL10‐induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo. Cancer Immunol Immunother CII. 2015;64(2):225‐235. doi:10.1007/s00262‐014‐1629‐5. Kremer V, Ligtenberg MA, Zendehdel R, et al. Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma. J Immunother Cancer. 2017;5(1):73. doi:10.1186/s40425‐017‐0275‐9. Muller N, Michen S, Tietze S, et al. Engineering NK cells modified with an EGFRvIII‐specific chimeric antigen receptor to overexpress CXCR4 improves immunotherapy of CXCL12/SDF‐1alpha‐secreting glioblastoma. J Immunother. 2015;38(5):197‐210. doi:10.1097/CJI.0000000000000082. Zykova TA, Zhu F, Wang L, et al. The T‐LAK cell‐originated protein kinase signal pathway promotes colorectal cancer metastasis. EBioMedicine. 2017;18:73‐82. doi:10.1016/j.ebiom.2017.04.003. Lu H, Xiao J, Ke C, et al. TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ. Cell Death Dis. 2019;10(8):583. doi:10.1038/s41419‐019‐1805‐9. Sachetto ATA, Rosa JG, Santoro ML. Rutin (quercetin‐3‐rutinoside) modulates the hemostatic disturbances and redox imbalance induced by Bothrops jararaca snake venom in mice. PLoS Negl Trop Dis. 2018;12(10):e0006774. doi:10.1371/journal.pntd.0006774. |
| معلومات مُعتمدة: | DFL20221201 Beijing Hospitals Authority's Ascent Plan; Laboratory for Clinical Medicine, Capital Medical University; Gynecological Tumor Precise Diagnosis and Treatment Innovation Studio |
| فهرسة مساهمة: | Keywords: drug and substance abuse; gerontopharmacology; gynecology and obstetrics; immunopharmacology; immunosuppressants |
| المشرفين على المادة: | 0 (Interleukin-2) 0 (N-(12-cyanoindolizino(2,3-b)quinoxalin-2-yl)thiophene-2-carboxamide) EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) 0 (Indolizines) 0 (Quinoxalines) |
| تواريخ الأحداث: | Date Created: 20240319 Date Completed: 20240417 Latest Revision: 20240417 |
| رمز التحديث: | 20240417 |
| DOI: | 10.1111/bcpt.14002 |
| PMID: | 38501576 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1742-7843 |
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| DOI: | 10.1111/bcpt.14002 |