Altamura Gennaro, Martano Manuela, Licenziato Luca, Maiolino Paola, Borzacchiello Giuseppe
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
Front Vet Sci. 2020 Mar 27;7:148. doi: 10.3389/fvets.2020.00148. eCollection 2020.
Telomerase activity contributes to cell immortalization by avoiding telomere shortening at each cell division; indeed, its catalytic subunit telomerase reverse transcriptase (TERT) is overexpressed in many tumors, including human oral squamous cell carcinoma (hOSCC). In these tumors, matrix metalloproteinases (MMPs), a group of zinc-dependent endopeptidases involved in cell migration, contribute to invasive potential of cancer cells. A proportion of hOSCC is associated with infection by high-risk human papillomavirus (HR-HPVs), whose E6 oncogene enhances TERT and MMPs expression, thus promoting cancer progression. Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor with highly invasive phenotype; however, studies on telomerase activity, TERT, and MMPs expression are scarce. In this study, we demonstrate telomerase activity, expression of TERT, and its transcriptional activator cMyc along with expression of MMP-1, -2, and -9 in FOSCC-derived cell lines SCCF2 and SCCF3, suggesting a contribution by these pathways in cell immortalization and invasion in these tumors. Recent studies suggest that a sub-group of FOSCC as well as SCCF2 and SCCF3 are associated with PV type-2 (FcaPV-2) infection. However, in this work, FcaPV-2 E6 gene knock-down caused no shift in either TERT, cMyc, or MMPs levels, suggesting that, unlike its human counterpart, the viral oncogene plays no role in their regulation.
端粒酶活性通过避免每次细胞分裂时端粒缩短来促进细胞永生化；实际上，其催化亚基端粒酶逆转录酶（TERT）在包括人类口腔鳞状细胞癌（hOSCC）在内的许多肿瘤中均过表达。在这些肿瘤中，基质金属蛋白酶（MMPs）是一组参与细胞迁移的锌依赖性内肽酶，有助于癌细胞的侵袭潜能。一部分hOSCC与高危人乳头瘤病毒（HR-HPVs）感染有关，其E6癌基因可增强TERT和MMPs的表达，从而促进癌症进展。猫口腔鳞状细胞癌（FOSCC）是一种具有高度侵袭性表型的恶性肿瘤；然而，关于端粒酶活性、TERT和MMPs表达的研究却很少。在本研究中，我们证明了FOSCC来源的细胞系SCCF2和SCCF3中端粒酶活性、TERT及其转录激活因子cMyc的表达，以及MMP-1、-2和-9的表达，表明这些途径在这些肿瘤的细胞永生化和侵袭中发挥了作用。最近的研究表明，FOSCC以及SCCF2和SCCF3的一个亚组与2型乳头瘤病毒（FcaPV-2）感染有关。然而，在这项研究中，FcaPV-2 E6基因敲低并未导致TERT、cMyc或MMPs水平发生变化，这表明，与其人类对应物不同，病毒癌基因在它们的调控中不起作用。
