also studied a different cohort, where the results for reverse transcriptase polymerase chain reaction (RT-PCR) and ISH correlated well [55]. characteristics of poor prognosis but this immunohistochemical MMP-14 determination does not seem to be an independent predictor of prognosis. Conclusions From this systematic review of the literature concerning MMP-14 in ovarian cancer it becomes clear that MMP-14 plays various important roles in the pathophysiology of ovarian cancer. The exact translation of these roles in the pathophysiology to the importance of MMP-14 in clinicopathological research in ovarian cancer and possible therapeutic role of anti-MMP-14 agents needs further elucidation. Supplementary Information The online version contains supplementary material available at 10.1186/s13048-021-00852-7. strong class=”kwd-title” Keywords: MMP-14, Ovarian cancer, Review, Cancer pathophysiology, Immunohistochemistry Introduction Ovarian cancer is known for its poor prognosis, due to the lack of effective screening methods and, therefore, its detection is usually in an advanced stage. Despite intensive treatment with surgery and chemotherapy and emerging options using targeted agents, ovarian cancer is still the leading cause of gynaecological cancer-related death in Europe and the United States. (http://gco.iarc.fr/today/home) [1] In search for new targets for treatment, matrixmetalloproteinases (MMPs) seem an attractive option. Members of the matrix metalloproteinase (MMP) family, also known as matrixins, belong to the metzincin superfamily. They are involved in the breakdown of extracellular matrix, not only in normal physiological processes, but also in pathological processes such as inflammation and cancer. MMPs are characterized by their zinc-binding site and the necessity of the containment of zinc for their enzymatic action [2]. Apart from their action as collagenases, gelatinases and stromelysins, various other roles for MMPs in cancer have been discerned. They have an effect at the tumour-cell level, intracellular actions in the nucleus [3] and in epithelial-to-mesenchymal transition and proliferation [4] and at the tumour micro-environment level, involvement in invasion, angiogenesis and metastasis [5]. In the context of inflammation, they influence T-cell inhibition and adhesion and macrophage inhibition [6]. Known and registered inhibitors of MMPs include the tetracyclines, of which doxycycline has been well studied [7]. Based on these results, the role of MMPs in ovarian cancer should be investigated further [8, 9]. So Purpureaside C far however, no therapeutic effect has been demonstrated for MMP inhibition in ovarian cancer [10, 11]. Since then, several new targeted agents against MMPs have been developed including antibodies and one of these new agents is a MMP-14 specific nanoprobe that facilitates in vivo detection of MMP-14 tumour cells. After administration of the nanoprobe, the tumour cells with nodules as small Purpureaside C as 125?m can be made visible with fluorescence [66]. In this review, we focus on MMP-14 (formerly identified as MT1-MMP) [12]. Most MMPs are secreted as inactive proproteins, which are activated when cleaved by extracellular proteinases [2]. However, MMP-14 is a member of the membrane-type MMP (MT-MMP) subfamily, which is characterised by a transmembrane domain, so that the MMPs are expressed at the cell surface rather than secreted [2]. In 1994, MMP-14 was the first membrane-bound MMP to be described [12] and its role on invasion and metastasis has been demonstrated in animal models [13, 14] Also, MMP-14 predicts prognosis in cancer in general according to a recent review [15]. MMP-14s main substrates are pro-MMP-2 and collagen I, but collagen II and III can also be cleaved be it to a lesser extent [2]. MMP-14 forms a dimer at the cell surface and a complex with MMP-2 and TIMP-2 (Tissue Inhibitor of MetalloProteinases 2) in order to activate MMP-2 [16C18]. It is also an enzyme for degradation of gelatine and cleavage of CD44 (a hyaluronan-receptor) [19]. MMP-14 expression varies depending on cancer type and is high in mesenchymal tumours, melanomas and brain tumours [4] and also found in hepatic tumours and in carcinomas including breast cancer [20, 21]. Though MMPs and ovarian cancer were reviewed before, [22] Purpureaside C no systematic review or meta-analysis on the Mouse Monoclonal to S tag role of MMP-14 alone in ovarian cancer has yet been published. Methods On 23 March 2020, we carried out a search in Pubmed on MMP-14 AND.