Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
Clin Chim Acta. 2022 Apr 1;529:25-33. doi: 10.1016/j.cca.2022.01.014. Epub 2022 Jan 24.
Incomplete surgical resection of invasive non-functional pituitary adenomas (NFPAs) produces a risk of the subsequent development of complications which will require treatment with powerful drugs and adjuvant radiotherapy.
The degree of invasiveness of NFPA can be established using biomarkers to help clinicians choose appropriate treatment for these patients.
This research explored transcriptomic and proteomic variations of non-invasive and invasive NFPAs, other forms of pituitary adenomas and evaluated exosomal genetic markers associated with these diseases. Increased expression of matrix metalloproteinase-1 (MMP1) and its formation in exosomes (exo-MMP1) were correlated with the characteristic invasiveness of NFPAs. Changes in the expression of MMP1 in the exosome was synchronized with transduction of NFPA cells. Enrichment of MMP1 stimulated migration, growth and angiogenesis in tumors through the protease-activated receptor-1 signaling pathway in cells.
The results revealed that MMP1 activity has obligatory actions in promoting tumor invasion and angiogenesis, and that the exosome-mediated regulatory pathway for MMP1 may be a novel therapeutic target.
侵袭性无功能性垂体腺瘤（NFPAs）的不完全手术切除会产生随后发生并发症的风险，这些并发症将需要使用强效药物和辅助放疗进行治疗。
可以使用生物标志物来确定 NFPA 的侵袭程度，以帮助临床医生为这些患者选择合适的治疗方法。
这项研究探讨了无侵袭性和侵袭性 NFPAs、其他形式的垂体腺瘤的转录组和蛋白质组变化，并评估了与这些疾病相关的外体遗传标志物。基质金属蛋白酶-1（MMP1）的表达增加及其在外体中的形成（exo-MMP1）与 NFPAs 的特征性侵袭性相关。MMP1 在细胞外体中的表达变化与 NFPA 细胞的转导同步。MMP1 的激活通过蛋白酶激活受体-1 信号通路刺激肿瘤中的迁移、生长和血管生成。
结果表明 MMP1 活性在促进肿瘤侵袭和血管生成方面具有强制性作用，外体介导的 MMP1 调节途径可能是一种新的治疗靶点。
