Pilot Project #1

摘要 这项临床前翻译方案的主要目标是确定红细胞巨噬细胞的作用。 蛋白(EMP)在肿瘤进展中的作用及其对结直肠癌的预后和预测价值 (CRCS)。在我们已发表的和初步的研究中，我们发现emp与红细胞有关。 去核、巨噬细胞发育、细胞生长和分化以及细胞黏附和迁移。这些 通路是癌症进展的标志。此外，我们的初步免疫组织化学(IHC) 对人类结直肠癌组织的评估表明，emp在肿瘤进展中的表达增加。 从腺瘤到原发腺癌再到转移癌。因此，我们假设emp是 参与了CRC的进展。为了验证这一假设，我们建议评估电磁脉冲相互作用的作用。 带有黏附分子，用于附着到细胞外膜(ECM)，用于分子串扰，用于效果 对肿瘤微环境的影响，以及对癌的进展的影响。这将通过三个目标来实现。AIM-1 将确定EMP与β-1整合素在局灶性粘连斑块中的相互作用及其参与 肿瘤进展；AIM-2将验证EMP与肌动蛋白细胞骨架在ECM功能和 而AIM-3将建立大肠癌中EMP的预后和预测价值。建议数 研究将表征Emp与β-1整合素的分子相互作用，确定Emp对 肌动蛋白细胞骨架和ECM的其他组件，识别有助于 肿瘤进展，并评估EMP在癌组织中的预测和预后价值。

SUMMARY The primary goal of this preclinical translational proposal is to determine the role of erythroblast macrophage protein (Emp) in tumor progression and to establish its prognostic and predictive value for colorectal cancers (CRCs). In our published and preliminary studies, we have discovered that Emp is involved in erythroblast enucleation, macrophage development, cell growth and differentiation, and cell adhesion and migration. These pathways are hallmarks of cancer progression. Additionally, our preliminary immunohistochemical (IHC) evaluations of human CRC tissues have demonstrated increasing expression of Emp in progression of adenomas to primary adenocarcinomas to metastatic carcinomas. Therefore, we hypothesize that Emp is involved in CRC progression. To test this hypothesis, we propose to evaluate the role of Emp interactions with adhesion molecules for attachment to extracellular membranes (ECM), for molecular cross-talk, for effects on the tumor microenvironment, and for progression of CRCs. This will be accomplished in three aims. Aim-1 will determine the interaction of Emp with β1 integrin within focal adhesion plaques and its involvement in tumor progression; Aim-2 will verify the interaction of Emp with the actin cytoskeleton in ECM functions and in metastasis; and Aim-3 will establish the prognostic and predictive value of Emp in CRCs. The proposed studies will characterize the molecular interactions of Emp with β1 integrin, ascertain the effects of Emp on the actin cytoskeleton and other components of the ECM, identify new molecular determinants that contribute to tumor progression, and assess the predictive and prognostic value of Emp in CRCs.