The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells.
The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells.
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干细胞因子/C-KIT受体途径增强了胰腺癌细胞的增殖和侵袭。
DOI：
10.1186/1476-4598-5-46
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发表时间：
2006-10-18
期刊：
影响因子：
37.3
通讯作者：
中科院分区：
文献类型：
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作者：
跨膜蛋白c-kit是一种受体酪氨酸激酶（KIT），并且KIT在实体瘤和血液恶性肿瘤如胃肠道间质瘤（GIST）、小细胞肺癌和慢性髓性白血病（CML）中表达。KIT在细胞增殖和分化中起关键作用，并代表GIST和CML的合理治疗靶点。在胰腺癌中，c-kit表达已通过免疫组织化学技术观察到。在这项研究中，我们使用五种胰腺癌细胞系检测c-kit表达对增殖和侵袭的影响。此外，评价了甲磺酸伊马替尼对干细胞因子（SCF）诱导的增殖和侵袭的抑制作用。最后，我们还分析了KIT和SCF在胰腺癌组织中的表达，并将结果与临床特征相关联。RT-PCR结果显示，胰腺癌细胞株PANC-1和SW 1990均表达c-kit mRNA。通过Western blot分析，c-kit蛋白也存在于这些品系中。在KIT阳性的胰腺癌细胞系中，SCF的加入显著增强了细胞的增殖和侵袭。相反，SCF在三个KIT阴性细胞系（BxPC-3、Capan-2和MIA PaCa-2）中没有增强增殖和侵袭。与对照组相比，5 μM甲磺酸伊马替尼显著抑制SCF增强的增殖。同样，SCF增强的侵袭能力被5 μM甲磺酸伊马替尼显著抑制。免疫组化结果显示，KIT在42例临床标本中有16例表达，且KIT表达与静脉系统侵犯显著相关。此外，同时表达KIT和SCF的患者生存率略低。我们的研究结果表明，SCF-KIT途径增强了KIT阳性胰腺癌细胞系的增殖和侵袭能力，并且增强的增殖和侵袭被甲磺酸伊马替尼抑制。我们认为c-kit酪氨酸激酶受体抑制剂有可能减缓KIT阳性胰腺癌的进展。
The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST), small-cell lung cancer and chronic myelogenous leukemia (CML). KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF)-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2). 5 μM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 μM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. We propose that inhibitors of c-kit tyrosine kinase receptor have the potential to slow the progression of KIT-positive pancreatic cancers.