CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer.
CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer.
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DOI：
10.1002/ijc.24040
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发表时间：
2009-02-15
影响因子：
6.4
通讯作者：
Guha, Sushovan
中科院分区：
文献类型：
--
作者：
Matsuo, Yoichi;Ochi, Nobuo;Sawai, Hirozumi;Yasuda, Akira;Takahashi, Hiroki;Fumahashi, Hitoshi;Takeyama, Hiromitsu;Tong, Zhimin;Guha, Sushovan
cxc趋化因子参与中性粒细胞、淋巴细胞和单核细胞的趋化。然而，这些趋化因子在肿瘤发生中的作用，特别是在肿瘤与其微环境的相互作用方面，尚未明确阐明。本研究的目的是分析CXCL8和CXCL12在胰腺癌（PaCa）肿瘤-基质相互作用中的协同作用。通过ELISA和RT-PCR，初步证实了cxc趋化因子在PaCa和基质细胞中分别有配体和受体的表达。我们分别通过MTS、Matrigel侵袭和血管生成实验检测了CXCL8和CXCL12在PaCa和人脐静脉内皮细胞（HUVECs）增殖/侵袭中的协同作用，以及通过肿瘤-基质相互作用在HUVEC管形成中的协同作用。我们在所有的PaCa细胞和成纤维细胞中检测到CXCR4的表达，而不是CXCR2。PaCa细胞分泌CXCL8，成纤维细胞分泌CXCL12。CXCL12可显著增强PaCa中CXCL8的生成，与PaCa共培养可显著增强成纤维细胞中CXCL12的生成。CXCL8增强HUVECs的增殖/侵袭，但不促进PaCa的增殖/侵袭。重组和paca衍生的CXCL8均能增强huvec与成纤维细胞共培养的管状形成。CXCL12增强HUVEC的增殖/侵袭和PaCa细胞的侵袭，但对HUVEC的管状形成没有影响。我们发现paca衍生的CXCL8和成纤维细胞衍生的CXCL12通过促进HUVEC增殖、侵袭和管形成来协同诱导体外血管生成。因此，相应的受体CXCR2和CXCR4是潜在的抗血管生成和抗转移治疗靶点。
CXC-chemokines are involved in the chemotaxis of neutrophils, lymphocytes and monocytes. However, role of these chemokines in tumorigenesis, especially with regard to interaction between tumor and its microenvironment, has not been clearly elucidated. The purpose of this study was to analyze the co-operative role of CXCL8 and CXCL12 in the tumor-stromal interaction in pancreatic cancer (PaCa). Using ELISA and RT-PCR, we initially confirmed the expression of ligands and receptors, respectively, of CXC-chemokines in PaCa and stromal cells. We examined the co-operative role of CXCL8 and CXCL12 in proliferation/invasion of PaCa and human umbilical vein endothelial cells (HUVECs), and in HUVEC tube-formations through tumor-stromal interaction by MTS, Matrigel invasion, and angiogenesis assays, respectively. We detected expression of CXCR4, but not CXCR2, in all PaCa cells and fibroblasts. PaCa cells secreted CXCL8, and fibroblast cells secreted CXCL12. CXCL8 production in PaCa was significantly enhanced by CXCL12, and CXCL12 production in fibroblasts was significantly enhanced by co-culturing with PaCa. CXCL8 enhanced proliferation/invasion of HUVECs but did not promote proliferation/invasion of PaCa. Both recombinant and PaCa-derived CXCL8 enhanced tube formation of HUVECs that were co-cultured with fibroblast cells. CXCL12 enhanced the proliferation/invasion of HUVECs and the invasion of PaCa cells but had no effect on tube formation of HUVEC. We showed that PaCa-derived CXCL8 and fibroblast-derived CXCL12 cooperatively induced angiogenesis in vitro by promoting HUVEC proliferation, invasion, and tube formation. Thus, corresponding receptors CXCR2 and CXCR4 are potential antiangiogenic and antimetastatic therapeutic targets in PaCa.
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影响因子：
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作者：
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通讯作者：
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