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Exosomes Derived from SW480-Resistant Colon Cancer Cells Are Promote Angiogenesis via BMP-2/Smad5 Signaling Pathway
Song Yang1, Lei Yao1, Xiaolong Wang1
1Department of General Surgery, Lu'an Hospital of Anhui Medical University, Lu'an Hospital of Anhui Province, Anhui 237005, China.
Background:
Multidrug resistance is the main cause of tumor recurrence and metastasis. Therefore, it is urgent to explore the mechanism and treatment of drug resistance of tumor cells. We aim to investigate the relationship between drug resistance and angiogenesis in SW480 colon cancer cells and the possible underlying mechanism.
Methods:
Exosomes were extracted from SW480-sensitive or SW480-resistant colon cancer cells (SW480/oxaliplatin). The CCK-8 assay, migration assay, tube formation assay, qPCR, and Western blotting were performed in human umbilical vein endothelial cells (HUVECs). The underlying mechanisms were detected by Western blotting assays and BMP-2 si-RNA silencing assay in vitro and in vivo.
Results:
The conditioned medium and exosomes of SW480/oxaliplatin cells promoted proliferation, migration, and tube formation of HUVECs. The expression of BMP-2 released by SW480/oxaliplatin exosomes was 2.3-folds higher than that by SW480 exosomes. Additionally, exosomal BMP-2 inhibiting the Smad signaling pathway induced the expression of vascular endothelial growth factor and CD31. Silencing of BMP-2 partly blocks the promoting effect of SW480/oxaliplatin exosomes on angiogenesis. Moreover, SW480/oxaliplatin cells increased the BMP-2 expression, consequently promoting angiogenesis in vivo.
Conclusions:
SW480-resistant colon cancer exosomes promoted angiogenesis via the BMP-2/Smad signaling pathway, which is potential for the novel treatment for antiangiogenic therapies in colon cancer.
Insights
Multidrug-resistant colon cancer exosomes promote angiogenesis through the BMP-2/Smad pathway. This finding offers potential for new anti-angiogenic therapies targeting colon cancer drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Multidrug resistance (MDR) in tumors drives recurrence and metastasis.
- Understanding MDR mechanisms is crucial for effective cancer treatment.
- This study investigates MDR and angiogenesis in colon cancer cells.
Purpose of the Study:
- To explore the link between drug resistance and angiogenesis in SW480 colon cancer cells.
- To elucidate the underlying molecular mechanisms involved in this process.
Main Methods:
- Exosomes were isolated from drug-sensitive and drug-resistant SW480 colon cancer cells.
- Assays included CCK-8, migration, and tube formation in HUVECs.
- Western blotting and BMP-2 siRNA were used to investigate mechanisms in vitro and in vivo.
Main Results:
- Exosomes from resistant cells promoted HUVEC proliferation, migration, and tube formation.
- Resistant cell exosomes showed 2.3-fold higher BMP-2 expression.
- Exosomal BMP-2 inhibited the Smad pathway, upregulating VEGF and CD31, promoting angiogenesis.
Conclusions:
- SW480-resistant colon cancer exosomes promote angiogenesis via the BMP-2/Smad signaling pathway.
- This pathway presents a potential target for novel anti-angiogenic therapies in colon cancer.
