College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Vet Pathol. 2019 Nov;56(6):826-839. doi: 10.1177/0300985819859873. Epub 2019 Jul 22.
Feline oral squamous cell carcinoma (FOSCC) is an aggressive malignancy with invasive and metastatic behavior. It is poorly responsive to chemotherapy and radiation. Neoplastic epithelial-mesenchymal transition (EMT) portends highly malignant behavior and enhances resistance to therapy. In transitioning to a more malignant phenotype, carcinoma stem cells undergo transformation mediated by expression of proteins, endowing them with mesenchymal properties advantageous to cell survival. The goal of the current study was to identify proteins associated with EMT in FOSCC. This study documents protein expression patterns in 10 FOSCC biopsies and 3 FOSCC cell lines (SCCF1, SCCF2, SCCF3), compatible with an EMT phenotype. As markers of EMT, P-cadherin, N-cadherin, vimentin, nuclear transcription factors Twist and Snail, hypoxia inducible factor 1α (HIF-1α), programmed death ligand 1, and vascular endothelial growth factor D, as well as E-cadherin, were examined using immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay. P-cadherin, Twist, HIF-1α, and programmed death ligand 1 were commonly expressed in biopsies and cell lines. N-cadherin, classically associated with EMT, was not highly expressed, and E-cadherin was coexpressed along with proteins characteristic of EMT in all specimens. Production of vascular endothelial growth factor A by cell lines, a process regulated by HIF-1α expression, was suppressed by the small-molecule inhibitor dasatinib. These data are consistent with EMT in FOSCC and shed light on cellular changes that could contribute to the aggressive behavior of FOSCC.
猫口腔鳞状细胞癌 (FOSCC) 是一种具有侵袭性和转移性的侵袭性恶性肿瘤。它对化疗和放疗反应不佳。肿瘤上皮间质转化 (EMT) 预示着高度恶性行为，并增强了对治疗的抵抗力。在向更恶性的表型转变过程中，癌干细胞通过表达蛋白质发生转化，赋予它们有利于细胞存活的间质特性。目前研究的目的是鉴定与 FOSCC 中的 EMT 相关的蛋白质。这项研究记录了 10 例 FOSCC 活检和 3 种 FOSCC 细胞系 (SCCF1、SCCF2、SCCF3) 中的蛋白质表达模式，这些细胞系与 EMT 表型一致。作为 EMT 的标志物，使用免疫组织化学、Western blot 和酶联免疫吸附试验检查了 P-钙黏蛋白、N-钙黏蛋白、波形蛋白、核转录因子 Twist 和 Snail、缺氧诱导因子 1α (HIF-1α)、程序性死亡配体 1 和血管内皮生长因子 D 以及 E-钙黏蛋白的表达。P-钙黏蛋白、Twist、HIF-1α 和程序性死亡配体 1 在活检和细胞系中普遍表达。N-钙黏蛋白与 EMT 经典相关，但表达不高，E-钙黏蛋白与所有标本中 EMT 特征蛋白共同表达。由 HIF-1α 表达调节的血管内皮生长因子 A 的产生由细胞系产生，小分子抑制剂 dasatinib 抑制该过程。这些数据与 FOSCC 中的 EMT 一致，并阐明了可能导致 FOSCC 侵袭性行为的细胞变化。
