Enhanced expression of keratinocyte growth factor and its receptor correlates with venous invasion in pancreatic cancer
Enhanced expression of keratinocyte growth factor and its receptor correlates with venous invasion in pancreatic cancer
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DOI：
10.2353/ajpath.2007.060935
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发表时间：
2007-06-01
影响因子：
6
通讯作者：
Tajiri, Takashi
中科院分区：
文献类型：
--
作者：
Cho, Kazumitsu;Ishiwata, Toshiyuki;Tajiri, Takashi
角质细胞生长因子（KGF）和KGF受体（KGFR）与癌症生长以及组织发育和修复有关。在这项研究中，我们检测了KGF和KGFR是否在人胰腺导管腺癌（PDAC）中起作用。KGFR mRNA在8个胰腺癌细胞系中表达，而KGF mRNA在7个细胞系中检测到，并且在MIA PaCa-2细胞中不存在。KGFR和KGF免疫反应分别位于41.5%和34.0%的患者的癌细胞中。KGFR或KGF免疫反应性与静脉浸润之间存在显著相关性，两种标记物的存在与静脉浸润、血管内皮生长因子（VEGF）-A表达和预后不良之间存在显著相关性。外源性KGF增加了MIA PaCa-2细胞中VEGF-A的表达和释放，并且稳定转染以过表达KGF-1的PANC-1细胞表现出增加的VEGF-A表达。此外，短发夹-KGFR转染MIA PaCa-2细胞减少了外源性KGF对VEGF-A表达的刺激作用。在KLM-1细胞中转染短发夹-KGFR降低了细胞中VEGF-A的表达。KGFR和KGF可能在PDAC中促进静脉侵袭和肿瘤血管生成，这增加了它们可能作为PDAC中抗血管生成策略的新治疗靶点的可能性。
Keratinocyte growth factor (KGF) and KGF receptor (KGFR) have been implicated in cancer growth as well as tissue development and repair. in this study, we examined whether KGF and KGFR have a role in human pancreatic ductal adenocarcinoma (PDAC). KGFR mRNA was expressed in eight pancreatic cancer cell lines, whereas the KGF mRNA was detected in seven of the cell lines and was absent in MIA PaCa-2 cells. KGFR and KGF immunoreactivity were localized in the cancer cells in 41.5 and 34.0% of patients, respectively. There was a significant correlation between KGFR or KGF immunoreactivity and venous invasion and a significant correlation between the presence of both markers and venous invasion, vascular endothelial growth factor (VEGF)-A expression, and poor prognosis. Exogenous KGF increased VEGF-A expression and release in MIA PaCa-2 cells, and PANC-1 cells stably transfected to over-express KGF-exhibited increased VEGF-A expression. Moreover, short hairpin-KGFR transfection in MIA PaCa-2 cells reduced the stimulatory effect of exogenous KGF on VEGF-A expression. Short hairpin-KGFR transfection in KLM-1 cells reduced VEGF-A expression in the cells. KGFR and KGF may act to promote venous invasion and tumor angiogenesis in PDAC, raising the possibility that they may serve as novel therapeutic targets in anti-angiogenic strategies in PDAC.