Patients with squamous cell carcinoma (SCC) have significantly lower survival upon the development of distant metastases. The extracellular matrix (ECM) is a consistent yet dynamic influence on the metastatic capacity of SCCs. The ECM encompasses a milieu of structural proteins, signaling molecules, and enzymes. Just over 40 years ago, the fibrous ECM glycoprotein laminin was identified. Roughly four decades of research have revealed a pivotal role of laminins in metastasis. However, trends in ECM alterations in some cancers have been applied broadly to all metastatic diseases, despite evidence that these characteristics vary by tumor type. We will summarize how laminins influence the SCC metastatic process exclusively. Enhanced laminin protein deposition occurs at the invasive edge of SCC tumors, which correlates with elevated levels of laminin-binding β1 integrins on SCC cells, increased MMP-3 presence, worse prognosis, and lymphatic dissemination. Although these findings are significant, gaps in knowledge of the formation of a premetastatic niche, the processes of intra- and extravasation, and the contributions of the ECM to SCC metastatic cell dormancy persist. Bridging these gaps requires novel in vitro systems and animal models that reproduce tumor–stromal interactions and spontaneous metastasis seen in the clinic. These advances will allow accurate assessment of laminins to predict responders to transforming growth factor-β inhibitors and immunotherapy, as well as potential combinatorial therapies with the standard of care. Such clinical interventions may drastically improve quality of life and patient survival by explicitly targeting SCC metastasis.

中文翻译：

---

重温转移性鳞状细胞癌中的层粘连蛋白和细胞外基质重塑：经过四十多年的研究，我们学到了什么？

鳞状细胞癌 (SCC) 患者在远处转移后的生存率显着降低。细胞外基质 (ECM) 对 SCC 的转移能力具有一致而动态的影响。ECM 包含结构蛋白、信号分子和酶的环境。就在 40 多年前，纤维状 ECM 糖蛋白层粘连蛋白被发现。大约四十年的研究揭示了层粘连蛋白在转移中的关键作用。然而，一些癌症中 ECM 改变的趋势已广泛应用于所有转移性疾病，尽管有证据表明这些特征因肿瘤类型而异。我们将总结层粘连蛋白如何专门影响 SCC 转移过程。增强的层粘连蛋白沉积发生在 SCC 肿瘤的浸润边缘，这与 SCC 细胞上层粘连蛋白结合 β1 整合素水平升高、MMP-3 存在增加、预后较差和淋巴传播相关。尽管这些发现意义重大，但在转移前生态位的形成、内渗和外渗过程以及 ECM 对 SCC 转移细胞休眠的贡献方面的知识差距仍然存在。弥合这些差距需要新的体外系统和动物模型来重现临床上看到的肿瘤-间质相互作用和自发转移。这些进展将允许准确评估层粘连蛋白，以预测对转化生长因子-β 抑制剂和免疫疗法的反应者，以及与护理标准的潜在组合疗法。