Vasohibin-1 expression is regulated by transforming growth factor-β/bone morphogenic protein signaling pathway...

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Vasohibin-1 is an endogenous angiogenesis inhibitor found in endothelial cells.
• Tumor-associated macrophages (TAMs) and transforming growth factor-β (TGF-β)/bone morphogenic protein (BMP) signaling are known promoters of tumor angiogenesis.
• The interplay between TAMs, TGF-β/BMP signaling, and vasohibin-1 expression in pancreatic cancer remains poorly understood.

Purpose of the Study:

• To investigate whether vasohibin-1 expression in pancreatic cancer cells is regulated by TGF-β/BMP signaling originating from TAMs.
• To explore the impact of TAMs on the expression of vasohibin-1, VEGF-A, and VEGF-C in pancreatic cancer cell lines.
• To elucidate the role of TGF-β and BMP signaling pathways in mediating these interactions.

Main Methods:

• Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify gene expression.
• TAMs were co-cultured with pancreatic cancer cell lines (Panc-1 and HPAF-II).
• Specific inhibitors (SB-431542 for TGF-β receptor 1, LDN193189 for BMP receptor 1) were used to block signaling pathways.

Main Results:

• TAMs co-cultured with pancreatic cancer cells upregulated TGF-β1, TGF-β2, BMP-4, and BMP-7 expression in TAMs.
• TAMs increased vasohibin-1, VEGF-A, and VEGF-C mRNA expression in pancreatic cancer cells.
• Inhibition of TGF-β or BMP receptors led to significantly upregulated vasohibin-1 expression but downregulated VEGF-C expression in cancer cells co-cultured with TAMs.

Conclusions:

• Vasohibin-1 expression in pancreatic cancer cells is indeed regulated by TGF-β/BMP signaling crosstalk with TAMs.
• These findings offer novel perspectives for developing anti-angiogenesis therapies targeting pancreatic cancer.
• Understanding this signaling axis provides a potential therapeutic avenue for controlling tumor vascularization.