scispace - formally typeset
Search or ask a question
Author

Manuel Feinauer

Other affiliations: University Hospital Heidelberg
Bio: Manuel Feinauer is an academic researcher from German Cancer Research Center. The author has contributed to research in topics: Cancer & Brain metastasis. The author has an hindex of 2, co-authored 2 publications receiving 13 citations. Previous affiliations of Manuel Feinauer include University Hospital Heidelberg.

Papers
More filters
Journal ArticleDOI
04 Mar 2021-Blood
TL;DR: In vivo multiphoton laser-scanning microscopy of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice, discovering a novel and specific mechanism that is crucial for brain colonization.

27 citations

Journal ArticleDOI
TL;DR: The data identify temporary slow-cycling breast cancer cells as the dominant source of brain and other metastases and demonstrates that this can lead to better understanding of BMIC-relevant pathways, including potential new approaches to prevent BM in patients.
Abstract: Specific biological properties of those circulating cancer cells that are the origin of brain metastases (BM) are not well understood. Here, single circulating breast cancer cells were fate-tracked during all steps of the brain metastatic cascade in mice after intracardial injection over weeks. A novel in vivo two-photon microscopy methodology was developed that allowed to determine the specific cellular and molecular features of breast cancer cells that homed in the brain, extravasated, and successfully established a brain macrometastasis. Those BM-initiating breast cancer cells (BMIC) were mainly originating from a slow-cycling subpopulation that included only 16% to 20% of all circulating cancer cells. BMICs showed enrichment of various markers of cellular stemness. As a proof of principle for the principal usefulness of this approach, expression profiling of BMICs versus non-BMICs was performed, which revealed upregulation of NDRG1 in the slow-cycling BMIC subpopulation in one BM model. Here, BM development was completely suppressed when NDRG1 expression was downregulated. In accordance, in primary human breast cancer, NDRG1 expression was heterogeneous, and high NDRG1 expression was associated with shorter metastasis-free survival. In conclusion, our data identify temporary slow-cycling breast cancer cells as the dominant source of brain and other metastases and demonstrates that this can lead to better understanding of BMIC-relevant pathways, including potential new approaches to prevent BM in patients. IMPLICATIONS: Cancer cells responsible for successful brain metastasis outgrowth are slow cycling and harbor stemness features. The molecular characteristics of these metastasis-initiating cells can be studied using intravital microscopy technology.

20 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: The biological machinery used by brain tumour stem cells to commandeer tissues in the intracranial space, evade immune responses and resist chemoradiotherapy is reviewed.

21 citations

Journal ArticleDOI
08 Sep 2021-Cells
TL;DR: The plasma glycoprotein von Willebrand factor (VWF) is exclusively synthesized in endothelial cells (ECs) and megakaryocytes, the precursor cells of platelets as discussed by the authors.
Abstract: The plasma glycoprotein von Willebrand factor (VWF) is exclusively synthesized in endothelial cells (ECs) and megakaryocytes, the precursor cells of platelets. Its primary function lies in hemostasis. However, VWF is much more than just a “fishing hook” for platelets and a transporter for coagulation factor VIII. VWF is a true multitasker when it comes to its many roles in cellular processes. In ECs, VWF coordinates the formation of Weibel–Palade bodies and guides several cargo proteins to these storage organelles, which control the release of hemostatic, inflammatory and angiogenic factors. Leukocytes employ VWF to assist their rolling on, adhesion to and passage through the endothelium. Vascular smooth muscle cell proliferation is supported by VWF, and it regulates angiogenesis. The life cycle of platelets is accompanied by VWF from their budding from megakaryocytes to adhesion, activation and aggregation until the end in apoptosis. Some tumor cells acquire the ability to produce VWF to promote metastasis and hide in a shell of VWF and platelets, and even the maturation of osteoclasts is regulated by VWF. This review summarizes the current knowledge on VWF’s versatile cellular functions and the resulting pathophysiological consequences of their dysregulation.

18 citations

Journal ArticleDOI
TL;DR: In a model of melanoma, treatment with low molecular weight heparin (LMWH) negatively regulated VWF secretion and attenuated tumor metastasis, and elevated plasma VWF levels constitute an independent biomarker for VTE risk.

12 citations

Journal ArticleDOI
TL;DR: In this article , the authors reviewed the evidence that shows how molecular alterations are involved in brain metastasis, majorly from breast cancer, lung cancer, and melanoma, and discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier and help to establish metastatic lesions in the uniquely distinct brain microenvironment.
Abstract: Abstract Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.

11 citations

Journal ArticleDOI
TL;DR: In this article , the potential clinical relevance of these interactions as biomarkers or as targets for anti-metastatic therapies was discussed, as well as potential clinical significance of the interactions between CTCs and different hematopoietic cells.

11 citations