乳酸通过调控血小板衍生微粒影响人肺腺癌生物学特性的机制研究
The Mechanism of Lactic Acid Regulating Platelet-Derived Microparticles to Affect the Biological Characteristics of Human Lung Adenocarcinoma
DOI: 10.12677/acm.2025.151039, PDF,   
作者: 刘红艳, 王海燕*:青岛大学附属医院输血科,山东 青岛;薛 杰:青岛大学附属医院输血科,山东 青岛;青岛胶州市中心医院输血科,山东 青岛
关键词: 肺腺癌乳酸血小板衍生微粒肿瘤微环境协同作用Lung Adenocarcinoma Lactate Platelet-Derived Particles Tumor Microenvironment Synergy
摘要: 乳酸作为肿瘤微环境中的关键代谢产物,在促进肿瘤进展方面发挥重要作用。本研究系统探讨了乳酸调控血小板衍生微粒(platelet-derived microparticles, PMPs)对人肺腺癌生物学行为的影响及其潜在机制。通过CCK-8实验和细胞划痕实验发现,不同浓度乳酸显著促进了A549细胞的增殖和迁移能力。此外,在乳酸环境下,PMPs进一步增强了细胞的增殖与迁移,并显著提升了肿瘤相关因子(如VEGF和TGF-β)的分泌水平。本研究揭示了乳酸环境下PMPs对肿瘤的协同作用,为进一步理解乳酸和PMPs在肿瘤微环境中的作用提供了新的视角。
Abstract: Lactate, as a pivotal metabolite in the tumour microenvironment, significantly contributes to tumour growth. This study comprehensively examined the impact of lactate-regulated platelet-derived microparticles (PMPs) on the biological behaviours of human lung adenocarcinoma and their probable causes. The CCK-8 assay and cell scratch assay revealed that varying doses of lactic acid considerably enhanced the proliferation and migratory capacity of A549 cells. Moreover, PMPs augmented cell proliferation and migration while markedly increasing the secretion levels of tumour-associated factors (e.g., VEGF and TGF-β) in a lactic acid environment. This study demonstrated the synergistic effects of PMPs on tumours within a lactic acid milieu, offering a novel perspective for comprehending the roles of lactic acid and PMPs in the tumour microenvironment.
文章引用:刘红艳, 薛杰, 王海燕. 乳酸通过调控血小板衍生微粒影响人肺腺癌生物学特性的机制研究[J]. 临床医学进展, 2025, 15(1): 274-281. https://doi.org/10.12677/acm.2025.151039

参考文献

[1] Gu, W., Liu, P., Tang, J., Lai, J., Wang, S., Zhang, J., et al. (2024) The Prognosis of TP53 and EGFR Co-Mutation in Patients with Advanced Lung Adenocarcinoma and Intracranial Metastasis Treated with EGFR-TKIs. Frontiers in Oncology, 13, Article 1288468. [Google Scholar] [CrossRef] [PubMed]
[2] Liu, C., Yu, H., Shen, X., Qiao, J., Wu, X., Chang, J., et al. (2019) Prognostic Significance and Biological Function of Lamina-Associated Polypeptide 2 in Non-Small-Cell Lung Cancer. OncoTargets and Therapy, 12, 3817-3827. [Google Scholar] [CrossRef] [PubMed]
[3] Yin, Q., Dai, L., Sun, R., Ke, P., Liu, L. and Jiang, B. (2022) Clinical Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials. Cancer Research and Treatment, 54, 803-816. [Google Scholar] [CrossRef] [PubMed]
[4] Boedtkjer, E. and Pedersen, S.F. (2020) The Acidic Tumor Microenvironment as a Driver of Cancer. Annual Review of Physiology, 82, 103-126. [Google Scholar] [CrossRef] [PubMed]
[5] Zhao, F., Wang, Z., Li, Z., Liu, S. and Li, S. (2022) Identifying a Lactic Acid Metabolism-Related Gene Signature Contributes to Predicting Prognosis, Immunotherapy Efficacy, and Tumor Microenvironment of Lung Adenocarcinoma. Frontiers in Immunology, 13, Article 980508. [Google Scholar] [CrossRef] [PubMed]
[6] Duan, B., Hu, J., Liu, H., Wang, Y., Li, H., Liu, S., et al. (2017) Genetic Variants in the Platelet‐Derived Growth Factor Subunit B Gene Associated with Pancreatic Cancer Risk. International Journal of Cancer, 142, 1322-1331. [Google Scholar] [CrossRef] [PubMed]
[7] Spakova, T., Janockova, J. and Rosocha, J. (2021) Characterization and Therapeutic Use of Extracellular Vesicles Derived from Platelets. International Journal of Molecular Sciences, 22, Article 9701. [Google Scholar] [CrossRef] [PubMed]
[8] Luan, H., Ye, F., Wu, L., Zhou, Y. and Jiang, J. (2014) Perioperative Blood Transfusion Adversely Affects Prognosis after Resection of Lung Cancer: A Systematic Review and a Meta-Analysis. BMC Surgery, 14, Article No. 34. [Google Scholar] [CrossRef] [PubMed]
[9] Żmigrodzka, M., Guzera, M., Miśkiewicz, A., Jagielski, D. and Winnicka, A. (2016) The Biology of Extracellular Vesicles with Focus on Platelet Microparticles and Their Role in Cancer Development and Progression. Tumor Biology, 37, 14391-14401. [Google Scholar] [CrossRef] [PubMed]
[10] Burnouf, T., Goubran, H.A., Chou, M., Devos, D. and Radosevic, M. (2014) Platelet Microparticles: Detection and Assessment of Their Paradoxical Functional Roles in Disease and Regenerative Medicine. Blood Reviews, 28, 155-166. [Google Scholar] [CrossRef] [PubMed]
[11] Singampalli, Z., Rajan, Y.R.D., Hemanth Rathod, R. and RajLaxmi, P.L.S. (2022) The Efficacy of Platelet-Rich Fibrin in the Management of Chronic Nonhealing Ulcers of the Lower Limb. Cureus, 14, e26829. [Google Scholar] [CrossRef] [PubMed]
[12] Li, N. (2015) Platelets in Cancer Metastasis: To Help the “Villain” to Do Evil: Platelets in Cancer Metastasis. International Journal of Cancer, 138, 2078-2087. [Google Scholar] [CrossRef] [PubMed]
[13] Placke, T., Örgel, M., Schaller, M., Jung, G., Rammensee, H., Kopp, H., et al. (2012) Platelet-Derived MHC Class I Confers a Pseudonormal Phenotype to Cancer Cells That Subverts the Antitumor Reactivity of Natural Killer Immune Cells. Cancer Research, 72, 440-448. [Google Scholar] [CrossRef] [PubMed]
[14] Sadallah, S., Schmied, L., Eken, C., Charoudeh, H.N., Amicarella, F. and Schifferli, J.A. (2016) Platelet-Derived Ectosomes Reduce NK Cell Function. The Journal of Immunology, 197, 1663-1671. [Google Scholar] [CrossRef] [PubMed]