Neutrophil Extracellular Traps (NETs) in Cancer Metastasis

Metastasis is the leading cause of cancer related morbidity and mortality. The metastatic process involves several identifiable biological stages, including tumor cell dissemination, intravasation, and the extravasation of circulating cancer cells to facilitate colonization at a distant site. Immune cell infiltration and inflammation within the tumor microenvironment coincide with tumor progression and metastatic spread and are thought to be the key mediators of this complex process. Amongst many infiltrating cells, neutrophils have recently emerged as an important player in fueling tumor progression, both in animal models and cancer patients. The production of Neutrophil Extracellular Traps (NETs) is particularly important in the pathogenesis of the metastatic cascade. NETs are composed of web-like DNA structures with entangled proteins that are released in response to inflammatory cues in the environment. NETs play an important role in driving tumor progression both in experimental and clinical models. In this review, we aim to summarize the current advances in understanding the role of NETs in cancer, with a specific focus on their role in promoting premetastatic niche formation, interaction with circulating cancer cells, and in epithelial to mesenchymal transition during cancer metastasis. We will furthermore discuss the possible role and different treatment options for targeting NETs to prevent tumor progression.

Recent Advances in Aptamer-Based Biosensors for Global Health Applications

Since aptamers were first reported in the early 2000s, research on their use for the detection of health-relevant analytical targets has exploded. This review article provides a brief overview of the most recent developments in the field of aptamer-based biosensors for global health applications. The review provides a description of general aptasensing principles and follows up with examples of recent reports of diagnostics-related applications. These applications include detection of proteins and small molecules, circulating cancer cells, whole-cell pathogens, extracellular vesicles, and tissue diagnostics. The review also discusses the main challenges that this growing technology faces in the quest of bringing these new devices from the laboratory to the market. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model

Clinically relevant brain metastases (BM) frequently form in cancer patients, with limited options for effective treatment. Circulating cancer cells must first permanently arrest in brain microvessels to colonize the brain, but the critical factors are not well understood. Here, in vivo multiphoton laser-scanning microscopy (MPLSM) of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor (VWF) deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice. Clot formation in brain microvessels occurred frequently (>95%) and specifically at intravascularly arrested cancer cells, allowing their long-time arrest. An extensive clot embedded approximately 20% of brain-arrested cancer cells, and those were more likely to successfully extravasate and form a macrometastasis. Mechanistically, tissue factor-mediated thrombin generation by cancer cells accounted for local activation of plasmatic coagulation in the brain. Thrombin inhibition by treatment with low-molecular weight heparin or dabigatran and an anti-VWF antibody prevented clot formation, cancer cell arrest, extravasation, and brain macrometastasis formation. In contrast, tumor cells were not able to directly activate platelets, and antiplatelet treatments did reduce platelet dispositions at intravascular cancer cells but did not reduce overall BM formation. In conclusion, our data shows that plasmatic coagulation is activated early by intravascular tumor cells in the brain, with subsequent clot formation, discovering a novel and specific mechanism that is crucial for brain colonization. Direct or indirect thrombin and VWF inhibitors emerge as promising drug candidates for BM prevention trials.

An efficient strategy for circulating tumor cell detection: surface-enhanced Raman spectroscopy

Circulating tumor cells (CTCs) are circulating cancer cells that shed from tumor tissue into blood vessels and circulate in the blood to invade other organs, which results in fatal metastases. Surface-enhanced Raman scattering (SERS) has great potentials in CTCs detection.

Continuously capturing circulating cancer cells

A wearable apheresis device allows for continuous and specific capture of circulating tumor cells.

COMPARATIVE EVALUATION OF THE RESULTS OF IMMUNOFLUORESCENCE AND HEMOFILTROCYTOLOGICAL RESEARCH IN CANCER PATIENTS

Immunofluorescence is a unique immunochemical method that combines the ability to conduct a detailed morphological analysis and use the specificity of the immunological reaction. The advantage of the immunofluorescence method is its high sensitivity and resolution. The immunofluorescence method was used to survey cell films of venous blood filtrate of cancer patients, and with usage of an apparatus for blood micro-screening, the successful extraction of circulating cancer cells was confirmed.