Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China.
J Interferon Cytokine Res. 2013 Aug;33(8):428-33. doi: 10.1089/jir.2012.0046. Epub 2013 May 7.
Vasohibin-1 has been detected in endothelial cells as an intrinsic angiogenesis inhibitor. Both tumor-associated macrophages (TAMs) and transforming growth factor-β (TGF-β)/bone morphogenic protein (BMP) signaling have been reported to promote angiogenesis in cancer. However, whether vasohibin-1 expression is regulated by TGF-β/BMP signaling between TAMs and cancer cells remains unclear. The expression of TGF-β1, TGF-β2, BMP-4, and BMP-7 in TAMs and the expression of vasohibin-1, vascular endothelial growth factor-A (VEGF-A), and VEGF-C in two pancreatic cancer cell lines (a nonmetastatic cell line Panc-1 and a distant metastatic cell line HPAF-II) were measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). The TGF-β receptor 1 and BMP receptor 1 were inhibited by the inhibitor SB-431542 and LDN193189, respectively. Thereafter, vasohibin-1, VEGF-A, and VEGF-C expression was detected by real-time RT-PCR. We found that the expression of TGF-β1, TGF-β2, BMP-4, and BMP-7 was upregulated in TAMs cocultured with pancreatic cancer cells. Vasohibin-1, VEGF-A, and VEGF-C mRNA expression in pancreatic cancer cells was upregulated by TAMs. Vasohibin-1 expression in pancreatic cancer cells cocultured with TAMs was upregulated significantly when TGF-β receptors or BMP receptors were inhibited, but VEGF-C expression was downregulated. Therefore, Vasohibin-1 expression is regulated by the TGF-β/BMP signaling between TAMs and pancreatic cancer cells. These results might shed a new light on the antiangiogenesis therapy in the pancreatic cancer.
血管抑素 1 已被发现在内皮细胞中作为一种内在的血管生成抑制剂。肿瘤相关巨噬细胞（TAMs）和转化生长因子-β（TGF-β）/骨形态发生蛋白（BMP）信号已被报道可促进癌症中的血管生成。然而，TAMs 和癌细胞之间的 TGF-β/BMP 信号是否调节血管抑素 1 的表达仍不清楚。通过实时逆转录聚合酶链反应（RT-PCR）测量 TAMs 中的 TGF-β1、TGF-β2、BMP-4 和 BMP-7 的表达以及两种胰腺癌细胞系（非转移性细胞系 Panc-1 和远处转移性细胞系 HPAF-II）中血管抑素 1、血管内皮生长因子-A（VEGF-A）和 VEGF-C 的表达。TGF-β 受体 1 和 BMP 受体 1 分别被抑制剂 SB-431542 和 LDN193189 抑制。此后，通过实时 RT-PCR 检测血管抑素 1、VEGF-A 和 VEGF-C 的表达。我们发现，与胰腺癌细胞共培养的 TAMs 中 TGF-β1、TGF-β2、BMP-4 和 BMP-7 的表达上调。TAMs 上调胰腺癌细胞中血管抑素 1、VEGF-A 和 VEGF-C mRNA 的表达。当抑制 TGF-β 受体或 BMP 受体时，与 TAMs 共培养的胰腺癌细胞中血管抑素 1 的表达显著上调，但 VEGF-C 的表达下调。因此，TAMs 和胰腺癌细胞之间的 TGF-β/BMP 信号调节血管抑素 1 的表达。这些结果可能为胰腺癌的抗血管生成治疗提供新的思路。
