肾上腺髓质素通过招募髓系单核细胞促进胰腺导管癌的生长

The stromal infiltration of myelomonocytic cells is one of the hallmarks of pancreatic ductal adenocarcinoma (PDAC). Experimental evidence for the causal relationship between the abundance of myelomonocytic cells and poor diagnosis has been well documented. ADM , as a peptide hormone, is overexpressed in several cancer types. Our preliminary experiment showed that pancreatic cancer expressed highest ADM levels compared to other cancer types. Furthermore, we also reported that macrophages which derived from myelomonocytic cells expressed all components of ADM receptor. So we suspect that pancreatic cancer may recruit myelomonocytic cells through secretion of ADM to promote tumor progression. During this project, we will make use of human cancer tissues, blood samples, cell lines and primary cells to explore the relationship between ADM and myelomonocytic cells in order to illuminate the new function of ADM in pancreatic cancer progression. In addition, we will explain the mechanisms how ADM recruits myelomonocytic cells to promote angiogenesis and tumor growth and how ADM influences the phenotype of myelomonocytic cells in molecular, cellular and animal levels. Taken together, our project intends to explore the new function of ADM in pancreatic cancer progression which will further reveal the possibility of ADM as a potential cancer treatment target. It will also provide theoretical basis for clinical cancer treatment in the future.

骨髓源单核细胞的大量侵袭是胰腺导管癌发生发展中的重要特征。研究报道在肿瘤组织中骨髓源单核细胞的丰度和肿瘤病人预后差存在相关性。肾上腺髓质素（ADM）是一种肽类激素，在多种癌症中过表达。我们预实验的结果显示ADM在胰腺癌中的表达水平最高，同时我们曾报道巨噬细胞表达ADM的受体，而巨噬细胞是由骨髓源单核细胞分化而来，这些结果提示胰腺癌很可能通过分泌ADM招募骨髓源单核细胞从而促进胰腺癌的进展。本项目将利用人的肿瘤组织、血浆样本和原代细胞来探索ADM和骨髓源单核细胞之间的关系，阐明ADM在胰腺癌生长过程中的新功能。另外我们将从分子、细胞和动物水平上来研究ADM招募骨髓源单核细胞从而促进血管新生和肿瘤生长的机制以及ADM对骨髓源单核细胞表型影响的作用机理。本课题将探索ADM在胰腺癌进展中的新功能，这有利于进一步揭示ADM作为癌症治疗靶点的可能性，为今后癌症治疗的临床应用提供理论依据。

骨髓源单核细胞的大量侵袭是胰腺导管癌发生发展中的重要特征。研究报道在肿瘤组织中骨髓源单核细胞的丰度和肿瘤病人预后差存在相关性。肾上腺髓质素（ADM）是一种肽类激素，在多种癌症中过表达。我们的结果显示ADM在胰腺癌中的表达水平最高，同时我们曾报道巨噬细胞表达ADM的受体，而巨噬细胞是由骨髓源单核细胞分化而来，这些结果提示胰腺癌很可能通过分泌ADM招募骨髓源单核细胞从而促进胰腺癌的进展。本项目利用人的肿瘤组织、血浆样本和原代细胞阐明了ADM和骨髓源单核细胞之间的关系，以及ADM在胰腺癌生长过程中的新功能。另外我们从分子、细胞和动物水平上研究了ADM招募骨髓源单核细胞、进而促进血管新生和肿瘤生长的机制以及ADM对骨髓源单核细胞表型影响的作用机理。本课题阐明了ADM在胰腺癌进展中的新功能，这有利于进一步揭示ADM作为癌症治疗靶点的可能性，为今后癌症治疗的临床应用提供理论依据。

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