The Effect of Ionizing Irradiation on the Autotaxin-Lysophasphatidic Acid Axis and Interleukin-6/8 Secretion in Different Breast Cancer Cell Lines.

IF 3 3区医学 Q2 HEALTH CARE SCIENCES & SERVICES Journal of Personalized Medicine Pub Date : 2024-09-12 DOI:10.3390/jpm14090968

Theresa Promny, Isabell Scherrer, Sheetal Kadam, Rafael Schmid, Tina Jost, Luitpold V Distel, Andreas Arkudas, Raymund E Horch, Annika Kengelbach-Weigand

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Abstract

Background: The Autotaxin (ATX)-lysophosphatidic acid (LPA) axis is involved in decreasing radiation sensitivity of breast tumor cells. This study aims to further elucidate the effect of irradiation on the ATX-LPA axis and cytokine secretion in different breast cancer cell lines to identify suitable breast cancer subtypes for targeted therapies.

Methods: Different breast cancer cell lines (MCF-7 (luminal A), BT-474 (luminal B), SKBR-3 (HER2-positive), MDA-MB-231 and MDA-MB-468 (triple-negative)) and the breast epithelial cell line MCF-10A were irradiated. The influence of irradiation on LPA receptor (LPAR) expression, ATX expression, and Interleukin (IL)-6 and IL-8 secretion was analyzed. Further, the effect of IL-6 and IL-8 on ATX expression of adipose-derived stem cells (ADSC) was investigated.

Results: Irradiation increased ATX and LPAR2 expression in MDA-MB-231 cells. Additionally, IL-6 secretion was enhanced in MDA-MB-231, and IL-8 secretion in MDA-MB-231 and MDA-MB-468. Stimulation of ADSC with IL-6 and IL-8 increased ATX expression in ADSC.

Conclusions: Targeting ATX or its downstream signaling pathways might enhance the sensitivity of triple-negative breast cancer cells to radiation. Further exploration of the interplay between irradiation, the ATX-LPA axis, and inflammatory cytokines may elucidate novel pathways for overcoming radioresistance and improving individual treatment outcomes.

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电离辐照对不同乳腺癌细胞株中自体释放素-嗜溶血酸轴和白细胞介素-6/8分泌的影响

背景：Autotaxin（ATX）-lysophosphatidic acid（LPA）轴参与降低乳腺癌细胞对辐射的敏感性。本研究旨在进一步阐明辐照对不同乳腺癌细胞系中 ATX-LPA 轴和细胞因子分泌的影响，从而确定适合靶向治疗的乳腺癌亚型：方法：对不同的乳腺癌细胞系（MCF-7（管腔A型）、BT-474（管腔B型）、SKBR-3（HER2阳性）、MDA-MB-231和MDA-MB-468（三阴性））以及乳腺上皮细胞系MCF-10A进行辐照。分析了辐照对 LPA 受体（LPAR）表达、ATX 表达、白细胞介素（IL）-6 和 IL-8 分泌的影响。此外，还研究了IL-6和IL-8对脂肪干细胞（ADSC）ATX表达的影响：结果：辐照增加了MDA-MB-231细胞中ATX和LPAR2的表达。此外，MDA-MB-231 细胞的 IL-6 分泌增强，MDA-MB-231 和 MDA-MB-468 细胞的 IL-8 分泌增强。用IL-6和IL-8刺激ADSC可增加ADSC中ATX的表达：结论：靶向 ATX 或其下游信号通路可能会提高三阴性乳腺癌细胞对辐射的敏感性。进一步探索辐照、ATX-LPA 轴和炎症细胞因子之间的相互作用可能会阐明克服放射抗性和改善个体治疗效果的新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Personalized Medicine Medicine-Medicine (miscellaneous)

CiteScore

4.10

自引率

0.00%

发文量

1878

审稿时长

11 weeks

期刊介绍： Journal of Personalized Medicine (JPM; ISSN 2075-4426) is an international, open access journal aimed at bringing all aspects of personalized medicine to one platform. JPM publishes cutting edge, innovative preclinical and translational scientific research and technologies related to personalized medicine (e.g., pharmacogenomics/proteomics, systems biology). JPM recognizes that personalized medicine—the assessment of genetic, environmental and host factors that cause variability of individuals—is a challenging, transdisciplinary topic that requires discussions from a range of experts. For a comprehensive perspective of personalized medicine, JPM aims to integrate expertise from the molecular and translational sciences, therapeutics and diagnostics, as well as discussions of regulatory, social, ethical and policy aspects. We provide a forum to bring together academic and clinical researchers, biotechnology, diagnostic and pharmaceutical companies, health professionals, regulatory and ethical experts, and government and regulatory authorities.