Suppression of endoplasmic reticulum stress-induced invasion and migration of breast cancer cells through the downregulation of heparanase (Retracted article. See vol. 48, pg. 188, 2021)
Suppression of endoplasmic reticulum stress-induced invasion and migration of breast cancer cells through the downregulation of heparanase (Retracted article. See vol. 48, pg. 188, 2021)
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通过下调乙酰肝素酶抑制内质网应激诱导的乳腺癌细胞侵袭和迁移
DOI：
10.3892/ijmm.2013.1292
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发表时间：
2013-05-01
影响因子：
5.4
通讯作者：
Jiang, Zhi Wen
中科院分区：
文献类型：
--
作者：
Li, Yang;Liu, Hao;Jiang, Zhi Wen
肿瘤转移是肿瘤发展的最终阶段，也是患者死亡的主要原因。肿瘤细胞突破由基底膜（BM）和细胞外基质（ECM）组成的天然屏障是肿瘤侵袭和转移的关键步骤。因此，保护这一屏障是降低死亡率的关键。乙酰肝素酶是哺乳动物的一种内切β-葡萄糖醛酸酶，能促进硫酸乙酰肝素（heparan sulfate，HS）的裂解，在肿瘤细胞的侵袭和转移中起重要作用。虽然化疗药物具有很强的抗肿瘤活性，但它们可能促进癌细胞的侵袭和迁移，正如在临床治疗过程中所观察到的那样。化学试剂可以诱导内质网（ER）应激，在这项研究中，我们使用阿霉素（ADM）和经典的ER应激诱导剂衣霉素（TM）。我们报告说，ER应激的激活参与了乳腺癌细胞的侵袭和迁移能力的增强，我们假设这种作用与乙酰肝素酶的激活有关。为了支持这一点，我们使用乙酰肝素酶抑制剂OGT 2115和低分子量肝素（LMWH）来抑制乙酰肝素酶的表达和活性，我们发现细胞的侵袭和迁移能力受到抑制。我们的研究结果表明，乙酰肝素酶抑制剂抑制乳腺癌细胞的侵袭和迁移诱导的ER压力，并提供了一个强有力的理由，为开发乙酰肝素酶为基础的治疗方法，用于预防化疗药物诱导的转移。
Tumor metastasis is the ultimate stage of cancer, and the primary cause of mortality in patients. Tumor cells breaking through the natural barrier consisting of the basement membrane (BM) and extracellular matrix (ECM) is the a crucial step in tumor invasion and metastasis. Thus, protecting this barrier is the key to reducing mortality. Heparanase is a mammalian endo-β-glucuronidase which has been found to promote the cleavage of heparan sulfate (HS), and plays a significant role in tumor cell invasion and metastasis. Although chemotherapeutic reagents have a strong antitumor activity, they may promote the invasion and migration of cancer cells, as has been observed during clinical treatment. Chemotherapeutic reagents can induce endoplasmic reticulum (ER) stress; in this study, we used adriamycin (ADM) and a classical ER stress inducer, tunicamycin (TM). We report that the activation of ER stress is involved in the enhanced invasion and migration ability of breast cancer cells and we hypothesized that this effect is associated with the activation of heparanase. In support of this, we used the heparanase inhibitor, OGT2115, and low molecular weight heparin (LMWH) to inhibit the expression and activity of heparanase, and we found that the invasion and migration ability of the cells was suppressed. Our findings demonstrate that heparanase inhibitors suppress breast cancer cell invasion and migration induced by ER stress, and provide a strong rationale for the development of heparanase-based therapeutics for the prevention of metastasis induced by chemotherapeutic reagents.