Methods of Experimental Modeling of Metastasis

One of the main problems of modern medicine is cancer, which is the second leading cause of death after cardiovascular disease. Malignant neoplasms have been known for a long time; however, their study still presents significant difficulties. Modeling of malignant processes in animals allow researchers to study tumors and the main patterns of malignant growth characteristic of animals and humans. The main cause of death in malignant neoplasms is the process of metastasis formation, which remains to be understood in detail. The study of metastatic processes is one of the most important tasks of oncology. To this end, various models of tumor metastasis are created. The article reviews literature data on the most popular models of metastasis in experimental conditions. The advantages and disadvantages of the main approaches to modeling metastasis are evaluated.

Metalloproteinases in Endometrial Cancer—Are They Worth Measuring?

Endometrial cancer is one of the most common gynecological malignancies, yet the molecular mechanisms that lead to tumor development and progression are still not fully established. Matrix metalloproteinases (MMPs) are a group of enzymes that play an important role in carcinogenesis. They are proteases involved in the degradation of the extracellular matrix (ECM) that surrounds the tumor and the affected tissue allows cell detachment from the primary tumor causing local invasion and metastasis formation. Recent investigations demonstrate significantly increased metalloproteinase and metalloproteinase inhibitor levels in patients with endometrial cancer compared to those with normal endometrium. In this review, we aim to show their clinical significance and possible use in the diagnosis and treatment of patients with endometrial cancer. We have critically summarized and reviewed the research on the role of MMPs in endometrial cancer.

Novel Methylation Biomarkers for Colorectal Cancer Prognosis

Colorectal cancer (CRC) comprises the third most common cancer worldwide and the second regarding number of deaths. In order to make a correct and early diagnosis to predict metastasis formation, biomarkers are an important tool. Although there are multiple signaling pathways associated with cancer progression, the most recognized are the MAPK pathway, p53 pathway, and TGF-β pathway. These pathways regulate many important functions in the cell, such as cell cycle regulation, proliferation, differentiation, and metastasis formation, among others. Changes in expression in genes belonging to these pathways are drivers of carcinogenesis. Often these expression changes are caused by mutations; however, epigenetic changes, such as DNA methylation, are increasingly acknowledged to play a role in the deregulation of oncogenic genes. This makes DNA methylation changes an interesting biomarkers in cancer. Among the newly identified biomarkers for CRC metastasis INHBB, SMOC2, BDNF, and TBRG4 are included, all of which are highly deregulated by methylation and closely associated with metastasis. The identification of such biomarkers in metastasis of CRC may allow a better treatment and early identification of cancer formation in order to perform better diagnostics and improve the life expectancy.

Wnt Signaling Pathway Is among the Drivers of Liver Metastasis

Liver metastasis, originating either from a primary liver or other cancer types, represent a large cancer-related burden. Therefore, studies that add to better understanding of its molecular basis are needed. Herein, the role of the Wnt signaling pathway in liver metastasis is outlined. Its role in hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT), motility, migration, metastasis formation, and other steps of the metastatic cascade are presented. Additionally, the roles of the Wnt signaling pathway in the liver metastasis formation of colorectal, breast, gastric, lung, melanoma, pancreatic, and prostate cancer are explored. The special emphasis is given to the role of the Wnt signaling pathway in the communication between the many of the components of the primary and secondary cancer microenvironment that contribute to the metastatic outgrowth in the liver. The data presented herein are a review of the most recent publications and advances in the field that add to the idea that the Wnt pathway is among the drivers of liver metastasis and that its targeting could potentially relieve liver metastasis–related complications.

Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review

Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.