2017年8月23日，北京大学口腔医院研究人员在国际学术期刊《Theranostics》在线发表了题为“Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma”的研究论文。腺样囊性癌好发于涎腺，且易发生肺转移导致预后不佳，如何早期诊治及预防是临床上的难题，研究发现涎腺腺样囊性癌细胞中的epiregulin通过外泌体影响肿瘤微环境及肺转移前微环境，促进涎腺腺样囊性癌肺转移。杨文文同学为该研究论文的第一作者，李盛林研究员、葛兮源副研究员为共同通讯作者。
Epiregulin是表皮生长因子家族的成员，通过与受体结合调节细胞如肿瘤上皮细胞和间质细胞的生长功能。近几年研究表明epiregulin是一个关键的促癌因子，在肺癌、肾癌和膀胱癌等多种肿瘤转移过程中发挥作用。
研究人员首次提出“exosomecrine”来定义通过exosomes的分泌方式，与其它分泌方式如autocrine、paracrine和juxtacrine不同，exosomecrine是细胞内的分子通过exosomes分泌到细胞外，再到达近处或远处的细胞，进而在细胞间交流物质和信息的形式。 Epiregulin通过包含在外泌体内的分泌方式“exosomecrine”进行细胞间物质交流，并可作用于远处，影响肺转移前微环境如提高肺血管的通透性，促进涎腺腺样囊性癌肺转移。此外Epiregulin通过外泌体这种分泌方式可影响肿瘤周围微环境如促进血管生成,促进肿瘤发展。
该研究首次发现外泌体在涎腺腺样囊性癌肺转移过程中发挥作用，揭示表皮生长因子成员epiregulin在涎腺腺样囊性癌肺转移过程中的作用机制，提示epiregulin可能作为涎腺腺样囊性癌的治疗靶点。
Epiregulin及富含epiregulin的外泌体促进鼠肺转移前微环境的形成及涎腺腺样囊性癌肺转移
原文链接：http://www.thno.org/v07p3700.htm
Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma
原文摘要
Salivary adenoid cystic carcinoma (SACC) is a peculiar malignant tumor, characterized by its slowbut inexorable growth, with a high incidence of lung metastasis and poor prognosis. Here, we showthe upregulated expression of EGFR ligand epiregulin in a subset of SACC cells correlates with lungmetastasis and unfavorable outcome in patients with SACC. We found that upregulation ofepiregulin in SACC cells induced epithelial-mesenchymal transition by regulating GLI1/E-cadherin.Elevated epiregulin increased the expression of pro-angiogenic factors, such as VEGFA, bFGF, andIL-8. We also show that epiregulin can be delivered via exosomes and was enriched in exosomesderived from epiregulin-overexpressing SACC cells. Furthermore, treating immunodeficient micewith these epiregulin-enriched exosomes greatly enhanced SACC metastasis to lung. Theseepiregulin-enriched exosomes significantly enhanced angiogenesis in the neighboring tumormicroenvironment and increased vascular permeability in the pre-metastaticlungmicroenvironment in vivo.Therefore,epiregulin, as well as epiregulin-containing exosomes, may bea novel target for controlling SACC lung metastasis.
