武汉云克隆科技股份有限公司

Abstract: Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX. Furthermore, the lungs of recipient mice injected with plasma from post-surgical colorectal cancer patients are more prone to metastatic seeding than mice injected with baseline plasma. Downregulation of LOX activity or levels reduces lung metastasis after surgery and increases survival, highlighting the potential of LOX inhibition in reducing the risk of metastasis following surgery.

摘要：手术仍然是治疗癌症最成功的疗法。然而，一些接受手术的早期疾病患者最终会屈服于远处转移。在这里，我们表明，响应手术，由于细胞外基质重塑，肺变得更容易转移。接受手术或接受手术的供体小鼠的血浆预处理的小鼠比对照早发生肺癌转移。缺氧的手术部位作为LOX的来源，增加赖氨酰氧化酶（LOX）活性和表达，原纤维胶原交联和粘着斑信号。此外，注射手术后结直肠癌患者的血浆的受体小鼠的肺比注射基线血浆的小鼠更容易发生转移性接种。 LOX活性或水平的下调减少了手术后的肺转移并提高了存活率，突出显示了LOX抑制在降低手术后转移风险中的潜力。

使用试剂原文信息：LOX expression in plasma and organ lysates (50 ug protein) was evaluated by ELISA (Cloud-Clone-Corp. SEC580Mu) in accordance with the manufacturer’s instructions.