Feline mammary carcinoma-derived extracellular vesicle promotes liver metastasis via sphingosine kinase-1-mediated premetastatic niche formation.

IF 2.7 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Laboratory Animal Research Pub Date : 2023-11-09 DOI:10.1186/s42826-023-00180-5

Yi-Chih Chang, Hao-Ping Liu, Hsiao-Li Chuang, Jiunn-Wang Liao, Pei-Ling Kao, Hsun-Lung Chan, Ter-Hsin Chen, Yu-Chih Wang

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Abstract

Background: Feline mammary carcinoma (FMC) is one of the most prevalent malignancies of female cats. FMC is highly metastatic and thus leads to poor disease outcomes. Among all metastases, liver metastasis occurs in about 25% of FMC patients. However, the mechanism underlying hepatic metastasis of FMC remains largely uncharacterized.

Results: Herein, we demonstrate that FMC-derived extracellular vesicles (FMC-EVs) promotes the liver metastasis of FMC by activating hepatic stellate cells (HSCs) to prime a hepatic premetastatic niche (PMN). Moreover, we provide evidence that sphingosine kinase 1 (SK1) delivered by FMC-EV was pivotal for the activation of HSC and the formation of hepatic PMN. Depletion of SK1 impaired cargo sorting in FMC-EV and the EV-potentiated HSC activation, and abolished hepatic colonization of FMC cells.

Conclusions: Taken together, our findings uncover a previously uncharacterized mechanism underlying liver-metastasis of FMC and provide new insights into prognosis and treatment of this feline malignancy.

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猫乳腺癌衍生的细胞外小泡通过鞘氨醇激酶-1介导的转移前小生境形成促进肝转移。

背景：猫乳腺癌（FMC）是最常见的母猫恶性肿瘤之一。FMC具有高度转移性，因此导致不良的疾病结果。在所有转移瘤中，约25%的FMC患者发生肝转移。然而，FMC肝转移的潜在机制在很大程度上仍不明确。结果：在本文中，我们证明了FMC衍生的细胞外小泡（FMC-EVs）通过激活肝星状细胞（HSC）来启动肝转移前小生境（PMN）来促进FMC的肝转移。此外，我们提供的证据表明，FMC-EV递送的鞘氨醇激酶1（SK1）对HSC的激活和肝PMN的形成至关重要。SK1的耗竭损害了FMC-EV中的货物分拣，EV增强了HSC的激活，并消除了FMC细胞的肝脏定殖。结论：总之，我们的研究结果揭示了FMC肝转移的一个先前未表征的机制，并为这种猫恶性肿瘤的预后和治疗提供了新的见解。

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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