缺氧腫瘤細胞以外泌體誘導巨噬細胞極化經由AMPK路徑以促使膀胱癌

林大欽

三總澎湖分院

Hypoxic Tumor-Derived Exosomes Induce Macrophage Polarization via AMPK to Promote in the Bladder Cancer

Ta Chin, Lin

Department of Surgery, Defence Medical Center, Penghu Branch, Taiwan

Purpose:

Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes play an important role in the communication between bladder Cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined . Materials and Methods: :Exosomes isolated from SV-HUC-1 cells under hypoxia conditions.

Abstract Objective: Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes play an important role in the communication between bladder Cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined .

Materials and Methods:

Exosomes isolated from SV-HUC-1 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exosomes. Flow cytometry, Western blot, wound healing and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of SV-HUC-1 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis.

Results:

Hypoxic induced of macrophages by activating AMPK pathway. Co-culture with hypoxia/exosomes-treated macrophages enhanced the migration, invasion, and epithelial mesenchymal transition (EMT) in SV-HUC-1 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and metastasis of SV-HUC-1 cells. Conclusion: Hypoxic induces macrophage polarization via AMPK pathway, and thus exerts a simulative effect on the growth and metastasis of bladder Cancer.

Conclusion:

In the present study, the results showed that hypoxia-exosomes induced macrophage polarization and therefore facilitated the migration and invasion of A549 cells. We found that hypoxia-exosomes derived from A549 cells could significantly elevate AMPK expression. Consistently, our data showed treatment with hypoxia-exosomes significantly increased the phosphorylation of AMPK in macrophages. Collectively, Our findings show that hypoxia-exosomes induced macrophage polarization via AMPK pathway and thus promotes lung tumor growth and metastasis. This study manifests hypoxia-exosomes as the possible targets for fighting against cancer progression and metastasis.