Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland, OH, USA.
Neoplasia. 2010 May;12(5):388-96. doi: 10.1593/neo.10166.
To survive and metastasize, tumors interact with surrounding tissues by secreting growth factors and cytokines. In return, surrounding host tissues respond by changing their secretome. Numerous factors theoretically function as therapeutic targets or biomarkers of cancer growth and metastatic risk. However, it is unclear if these factors are tumor-derived or actually represent the host defense. To analyze the concentrations of tumor- and microenvironment-derived factors associated with neoplastic growth, we used ELISA-based arrays specific for murine or human proteins to establish a profile of tumor- or host-derived factors circulating in the plasma or within the platelets upon human tumor implantation into mice. Many factors characterized as tumor-derived were actually secreted by host tissues. This study uncovered the origin of various cytokines and revealed their circulation methods. We found that tumor-produced cytokines are predominantly sequestered in platelets. Sequestered proteins are protected from degradation and, thus, may be functional at metastatic sites. These findings identify tumor-specific targets for the detection and prevention of tumor growth and metastasis. As predicted by our model, monocyte chemotactic protein 1 and tumor necrosis factor alpha may be biomarkers for human cancers. Thus, our study identified several potential biomarkers that might be predictive of prostate cancer.
为了生存和转移，肿瘤通过分泌生长因子和细胞因子与周围组织相互作用。作为回应，周围的宿主组织通过改变它们的分泌组来做出反应。许多因素从理论上可以作为癌症生长和转移风险的治疗靶点或生物标志物。然而，目前还不清楚这些因素是肿瘤来源的，还是实际上代表了宿主防御。为了分析与肿瘤生长相关的肿瘤和微环境来源的因子浓度，我们使用了基于 ELISA 的针对鼠或人蛋白的阵列，以建立在人类肿瘤植入小鼠后在血浆或血小板中循环的肿瘤或宿主来源因子的图谱。许多被认为是肿瘤来源的因子实际上是由宿主组织分泌的。这项研究揭示了各种细胞因子的来源，并揭示了它们的循环方式。我们发现，肿瘤产生的细胞因子主要被血小板隔离。被隔离的蛋白质免受降解，因此，在转移部位可能具有功能。这些发现为检测和预防肿瘤生长和转移确定了肿瘤特异性的靶标。正如我们的模型所预测的，单核细胞趋化蛋白 1 和肿瘤坏死因子-α可能是人类癌症的生物标志物。因此，我们的研究确定了几个可能预测前列腺癌的潜在生物标志物。
