Epithelial–mesenchymal transition (EMT) has recently been associated with tumor progression, metastasis, and chemotherapy resistance in several tumor types. We performed a differential gene expression analysis comparing paclitaxel-resistant vs. paclitaxel-sensitive breast cancer cells that showed the upregulation of EDIL3 (EGF Like Repeats and Discoidin I Like Domains Protein 3). This gene codifies an extracellular matrix protein that has been identified as a novel regulator of EMT, so we studied its role in tumor progression and paclitaxel response. Our results demonstrated that EDIL3 expression levels were increased in paclitaxel-resistant breast and prostate cancer cells, and in subsets of high-grade breast and prostate tumors. Moreover, we observed that EDIL3 modulated the expression of EMT markers and this was impaired by cilengitide, which blocks the EDIL3–integrin α_Vβ₃ interaction. EDIL3 knockdown reverted EMT and sensitized cells to paclitaxel. In contrast, EDIL3 overexpression or the culture of cells in the presence of EDIL3-enriched medium induced EMT and paclitaxel resistance. Adding cilengitide resensitized these cells to paclitaxel treatment. In summary, EDIL3 may contribute to EMT and paclitaxel resistance through autocrine or paracrine signaling in cancer cells. Blockade of EDIL3–integrin α_Vβ₃ interaction by cilengitide restores sensitivity to paclitaxel and reverts EMT in paclitaxel-resistant cancer cells. Combinations of cilengitide and taxanes could be beneficial in the treatment of subsets of breast and prostate cancers.

最近，上皮-间质转化（EMT）与多种肿瘤类型的肿瘤进展、转移和化疗耐药相关。我们进行了差异基因表达分析，比较了紫杉醇耐药性和紫杉醇敏感性乳腺癌细胞，结果显示EDIL3（EGF 样重复序列和盘状蛋白 I 样结构域蛋白 3）上调。该基因编码一种细胞外基质蛋白，该蛋白已被确定为 EMT 的新型调节因子，因此我们研究了它在肿瘤进展和紫杉醇反应中的作用。我们的结果表明，在紫杉醇耐药的乳腺癌和前列腺癌细胞以及高级别乳腺癌和前列腺肿瘤的子集中，EDIL3 表达水平升高。此外，我们观察到 EDIL3 调节 EMT 标志物的表达，而西仑吉肽会损害这种表达，西仑吉肽阻断 EDIL3-整合素 α _V β ₃相互作用。EDIL3 敲低可恢复 EMT 并使细胞对紫杉醇敏感。相反，EDIL3 过表达或在富含 EDIL3 的培养基存在下培养细胞会诱导 EMT 和紫杉醇耐药。添加西仑吉肽使这些细胞对紫杉醇治疗重新敏感。总之，EDIL3 可能通过癌细胞中的自分泌或旁分泌信号传导导致 EMT 和紫杉醇耐药。西仑吉肽阻断 EDIL3-整合素 α _V β ₃相互作用可恢复紫杉醇耐药癌细胞对紫杉醇的敏感性并恢复 EMT。西仑吉肽和紫杉烷类药物的组合可能有益于治疗乳腺癌和前列腺癌。