Expression and Function of a Disintegrin and Metalloproteinases in Cancer-Associated Fibroblasts of Colorectal Cancer
Expression and Function of a Disintegrin and Metalloproteinases in Cancer-Associated Fibroblasts of Colorectal Cancer
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DOI：
10.1159/000504087
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发表时间：
2020-01-01
期刊：
影响因子：
3.2
通讯作者：
Ueno, Hideki
中科院分区：
文献类型：
--
作者：
Mochizuki, Satsuki;Ao, Tadakazu;Ueno, Hideki
背景：癌组织由癌细胞和间质组成，后者决定癌组织的微环境。我们最近报道，结直肠癌（CRC）侵袭前沿的促纤维增生反应（DR）模式是一个有希望的预后指标。然而，DR 形成的分子机制及其对患者预后的影响仍不清楚。摘要：由细胞外基质（ECM）、可溶性因子（生长因子/细胞因子/细胞因子）和基质细胞组成的肿瘤组织微环境控制着肿瘤的生长和扩散。在基质细胞中，癌症相关成纤维细胞 (CAF) 在癌症组织微环境的发展中发挥着关键作用，它们负责 DR 的形成。 CAF 表达解整合素和金属蛋白酶 (ADAM)，调节癌组织微环境因素。我们从 CRC 患者的结肠组织中分离出 CAF 和正常成纤维细胞，并对其进行表征。 CAF 显示多种 ADAM 物种（包括 ADAM9、ADAM10、ADAM12 和 ADAM17）的表达增加，并且在 ECM 包被的板上表达进一步增加。我们使用 CAF 和 CRC 细胞进行的体外和体内研究表明，ADAM 表达与形态学 DR 类别相关，ADAM 可能通过 CRC 中的肿瘤增殖影响癌症恶性肿瘤。关键信息：这篇综述总结了目前关于 ADAM 在癌症中的知识，并主要通过关注 ADAM 描述了我们最近关于 DR 分子生物学背景的发现。
Background: Cancer tissues consist of cancer cells and stroma, the latter of which dictates cancer tissue microenvironment. We recently reported that the desmoplastic reaction (DR) pattern at the invasive front in colorectal cancer (CRC) is a promising prognostic indicator. However, the molecular mechanisms of DR formation and contribution to patients' prognosis remain unclear. Summary: The tumor tissue microenvironment composed of extracellular matrix (ECM), soluble factors (growth factors/cytokine/cytokine), and stromal cells controls tumor growth and spread. Among stromal cells, cancer-associated fibroblasts (CAFs) play a key role in development of the cancer tissue microenvironment, and they are responsible for DR formation. CAFs express a disintegrin and metalloproteinases (ADAMs), which modulate cancer tissue microenvironmental factors. We isolated CAFs and normal fibroblasts from colon tissues of patients with CRC and characterized them. CAFs showed the increased expression of several ADAM species including ADAM9, ADAM10, ADAM12, and ADAM17, and the expression was further increased on the ECM-coated plates. Our in vitro and in vivo studies using CAFs and CRC cells suggest that ADAM expression is associated with the morphological DR category, and ADAMs may affect cancer malignancy through tumor proliferation in CRC. Key Message: This review summarizes the present knowledge on ADAMs in cancer and describes our recent findings regarding the molecular biological background of DR mainly by focusing on ADAMs.