Changes in the Extracellular Matrix in Endometrial and Cervical Cancer: A Systematic Review

Abstract

Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.

Engineering a three-dimensional multilayer multicellular model of endometrial cancer for high throughput drug screening and novel treatment methods

“…In addition to Col IV and laminin, fibronectin is a major component of the endometrial cancer tumor microenvironment and has been previously demonstrated to promote endometrial cancer growth and invasion. 1,17,35 We evaluated fibronectin from 0.125 to 0.175 mg/mL and found that the concentration that maximized endothelial and endometrial cancer metastatic behavrior was 0.17 mg/mL, at the higher end of our tested range. All three of these ECM components had significant interactions with each other as well as ECM components in the bottom hydrogel, again highlighting the importance of capturing the layered architecture and multicellular nature of the endometrial cancer tumor microenvironment.…”

“…Endometrial cancer, the most common gynecological cancer in developed countries and the sixth most common type of cancer worldwide, presents a significant healthcare challenge. 1,2 In 2023, 66,200 women were diagnosed with this disease and over 13,000 women died from endometrial cancer in the United States alone. 3 While early-stage endometrial cancer can be effectively treated with surgery, chemotherapy, and radiation, advanced stages often have poor prognoses, with a five year survival rate under 20%, primarily due to metastasis.…”

Dietary Polyphenols Effects on Focal Adhesion Plaques and Metalloproteinases in Cancer Invasiveness

“…The main proteins involved in cell invasion are MMPs, found in the ECM, and cadherins found at the cell membrane [ 253 ]. Specifically, MMPs degrade ECM proteins, while changes in cadherins expression levels contribute to the EMT, also important to start the cell’s invasion process [ 254 ]. The FAP is also fundamental for cell survival thanks to the presence of multiple protein kinases, such as Akt, mTOR, PI3K and MAPKs, that start pro-survival signaling cascades [ 255 ].…”

The nano-revolution in the diagnosis and treatment of endometriosis

“…89 The Extracellular matrix degradation play also an important role the pathogenesis of endometriosis. 90 Singh et al developed a dual drug-loaded PLGA NPs that combines the anti-angiogenic and antioxidant properties of epigallocatechin gallate (EGCG) and the matrix metalloproteinase inhibitory activity of antibiotic doxycycline (Dox) 91 in order to improve and reduce the limitations when they are used in their native forms. The novelty of this nanosystem is given by the delivery of two different agents (Dox and EGCG) in a single vehicle: the dual agent-NPs was more efficient at reducing levels of metalloproteinase (MMPs) and angiogenic factors in mice with endometriosis than single drug-loaded NPs.…”