Bui Thao Phuong, Hoang Anh Ngoc, Le Phuong Lan, Pham Bich Thi, Nguyen Linh Thi Tu, Do Ha Minh, Ta To Van, Trinh Thai Hong
Department of Biology and Key Laboratory of Enzyme and Protein Technology, College of Science, Vietnam National University, Hanoi 10000, Vietnam.
Department of Anatomical Pathology-Cytopathology, Vietnam National Cancer Hospital, Hanoi 10000, Vietnam.
Oncol Lett. 2017 Apr;13(4):2097-2104. doi: 10.3892/ol.2017.5680. Epub 2017 Feb 6.
Matrix metalloproteinases (MMPs), a family of endopeptidases also known as gelatinases, have been reported to affect the acquisition of the cell proliferative, cell invasive and metastatic phenotype of several types of cancer. In particular, the gelatinases MMP-2 and -9 have been revealed to facilitate tumor growth and invasion in patients with colorectal cancer (CRC). However, it is not known whether the gelatinase activity of MMP-2 and -9 is also elevated in Vietnamese patients with CRC. The activity of MMP-2 and -9 in the tissue samples of 103 patients with CRC was evaluated by gelatin zymography and quantified using ImageJ. The association between the level of activity of MMP-2 and -9 and various clinicopathological factors was analyzed, and Chisio BioPAX Editor software was used to visualize the biological pathways regulating the activity of the MMPs. The present study noticed significantly increased activity of active MMP-2 and MMP-9 in tumor tissues (P<0.01), and significantly decreased levels of pro-form MMP-2 and MMP-9 in tumor tissues (P<0.01), compared with that in adjacent tissues in patients with CRC. A correlation between the normalized different activity of MMP-2 and -9 and various clinicopathological features was observed. Furthermore, bioinformatics analysis indicated that the alteration in the activity of MMP-2 and MMP-9 may have been controlled by biological pathways involving the tissue inhibitors of metalloprotease-2 and -1. These findings indicate that the activity of the gelatinases MMP-2 and -9 affects the tumor progression and metastasis of patients with CRC, providing a potential novel approach for determining the prognosis of CRC.
基质金属蛋白酶（MMPs）是一类也被称为明胶酶的内肽酶，据报道，它们会影响多种癌症的细胞增殖、侵袭和转移表型的获得。特别是，已发现明胶酶MMP - 2和 - 9可促进结直肠癌（CRC）患者的肿瘤生长和侵袭。然而，尚不清楚在越南CRC患者中MMP - 2和 - 9的明胶酶活性是否也会升高。通过明胶酶谱法评估了103例CRC患者组织样本中MMP - 2和 - 9的活性，并使用ImageJ进行定量分析。分析了MMP - 2和 - 9的活性水平与各种临床病理因素之间的关联，并使用Chisio BioPAX Editor软件可视化调节MMPs活性的生物学途径。本研究发现，与CRC患者的癌旁组织相比，肿瘤组织中活性MMP - 2和MMP - 9的活性显著增加（P<0.01），而肿瘤组织中前体形式的MMP - 2和MMP - 9水平显著降低（P<0.01）。观察到MMP - 2和 - 9的标准化差异活性与各种临床病理特征之间存在相关性。此外，生物信息学分析表明，MMP - 2和MMP - 9活性的改变可能受涉及金属蛋白酶组织抑制剂 - 2和 - 1的生物学途径控制。这些发现表明，明胶酶MMP - 2和 - 9的活性影响CRC患者的肿瘤进展和转移，为确定CRC的预后提供了一种潜在的新方法。
