Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Transl Oncol. 2011 Apr 1;4(2):83-91. doi: 10.1593/tlo.10202.
There is an urgent need to develop novel markers of pancreatic cancer to facilitate early diagnosis. Pancreatic carcinoma is characterized by marked stroma formation with a high number of infiltrating tumor-associated macrophages (TAMs) that originate from circulating mononuclear cells (MNCs). We hypothesized that differential analysis of protein expression and phosphorylation in circulating MNCs from healthy nude mice and nude mice bearing orthotopic human pancreatic cancer would identify a surrogate marker of pancreatic cancer. These differences were analyzed by two-dimensional gel electrophoresis followed by Western blot analysis using antibody against phosphorylated tyrosine proteins (pY). Protein and phosphorylated protein spots of interest were identified by mass spectrometry and validated by Western blot analysis as candidate markers for pancreatic cancer. We found that the expression and phosphorylation of Src family proteins were significantly higher in circulating MNCs from mice bearing pancreatic cancer than in circulating MNCs from healthy mice. TAMs in mice with pancreatic tumors also had higher Src family protein expression and phosphorylation than resident macrophages in the pancreas of healthy mice. The expression and phosphorylation of Src family proteins were correlated with tumor weight; however, increased Src expression and phosphorylation also occurred in MNCs from mice with chronic pancreatitis. This is the first report to explore novel pancreatic tumor markers in circulating MNCs. Although the specificity of the marker for pancreatic cancer was low, it could be used to monitor the disease or to select high-risk patients with chronic pancreatitis.
目前迫切需要开发新的胰腺癌标志物，以促进早期诊断。胰腺癌的特征是基质形成明显，浸润的肿瘤相关巨噬细胞（TAMs）数量众多，这些 TAMs 来源于循环单核细胞（MNC）。我们假设对来自健康裸鼠和荷人原位胰腺癌裸鼠的循环 MNC 中的蛋白质表达和磷酸化进行差异分析，将鉴定出胰腺癌的替代标志物。使用针对磷酸化酪氨酸蛋白（pY）的抗体通过二维凝胶电泳和 Western blot 分析来分析这些差异。通过质谱鉴定感兴趣的蛋白质和磷酸化蛋白质斑点，并通过 Western blot 分析进行验证，作为胰腺癌的候选标志物。我们发现，与健康小鼠的循环 MNC 相比，荷胰腺癌小鼠的循环 MNC 中 Src 家族蛋白的表达和磷酸化显著升高。胰腺肿瘤小鼠的 TAMs 中 Src 家族蛋白的表达和磷酸化也高于健康小鼠胰腺中的固有巨噬细胞。Src 家族蛋白的表达和磷酸化与肿瘤重量相关；然而，慢性胰腺炎小鼠的 MNC 中也出现了 Src 表达和磷酸化的增加。这是首次在循环 MNC 中探索新型胰腺肿瘤标志物的报道。尽管该标志物对胰腺癌的特异性较低，但它可用于监测疾病或选择慢性胰腺炎的高危患者。
