Abstract
Gynecological illness accounts for around 4.5% of the global disease burden, which is higher than other key global health concerns such as malaria (1.04%), TB (1.9%), ischemic heart disease (2.2%), and maternal disorders (3.5%). Gynecological conditions in women of reproductive age are linked to both in terms of diagnosis and treatment, especially in low-income economies, which poses a serious social problem. A greater understanding of health promotion and illness management can help to prevent diseases in gynecology. Due to the lack of established biomarkers, the identification of gynecological diseases, including malignancies, has proven to be challenging in most situations, and histological exams remain the gold standard. Metalloproteinases (MMPs, ADAMs, ADAMTSs) and their endogenous inhibitors (TIMPs) modulate the protease-dependent bioavailability of local niche components (e.g., growth factors), matrix turnover, and cellular interactions to govern specific physical and biochemical characteristics of the environment. Matrix metalloproteinases (MMPs), A Disintegrin and Metalloproteinase (ADAM), and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) are zinc-dependent endopeptidases that contribute significantly to the disintegration of extracellular matrix proteins and shedding of membrane-bound receptor molecules in several diseases, including arthritis. MMPs are noteworthy genes associated with cancer development, functional angiogenesis, invasion, metastasis, and immune surveillance evasion. These genes are often elevated in cancer and multiple benign gynecological disorders like endometriosis, according to research. Migration through the extracellular matrix, which involves proteolytic activity, is an essential step in tumor cell extravasation and metastasis. However, none of the MMPs’ expression patterns, as well as their diagnostic and prognostic potential, have been studied in a pan-cancer context. The latter plays a very important role in cell signaling and might be used as a cancer treatment target. ADAMs are implicated in tumor cell proliferation, angiogenesis, and metastasis. This review will focus on the contribution of the aforementioned metalloproteinases in regulating gynecological disorders and their subsequent manipulation for therapeutic intervention.
Highlights
Gynecological malignancies, mainly comprised of cervical, ovarian, and endometrial cancers, contribute immensely to the worldwide cancer load, with cervical cancer being the fourth most common cancer in women (Bray et al, 2018)
In contrast to a normal inflammatory response, which is characterized by a temporally limited increase in inflammatory signals that resolves once the threat has passed, systemic chronic inflammation (SCI) is a low-grade, prolonged state of the activated immune response leading to changes in normal cellular morphology
Studies revealed that matrix metalloproteinase (MMP)-1 knockdown results with an increased E-cadherin and decreased vimentin expression in cervical cancer cell lines which leads to a decrease in cell proliferation, migration, and invasion which suggests that MMP-1 plays a crucial role in regulating epithelial-to-mesenchymal transition (EMT) (Tian et al, 2018)
Summary
Gynecological malignancies, mainly comprised of cervical, ovarian, and endometrial cancers, contribute immensely to the worldwide cancer load, with cervical cancer being the fourth most common cancer in women (Bray et al, 2018). Infiltrating immune cells and inflammatory mediators like cytokines/chemokines and growth factors contribute to cell proliferation and migration in multiple tumors by upregulating metalloproteinases. MMP-9, and -2, and urokinase plasminogen activators play a crucial role in degrading the ECM and enabling metastatic cells to enter the vasculature and move into the target organ, resulting in tumor metastasis of cervical malignancies (Ye et al, 2020).
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