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International Journal of Molecular... Apr 2023Cancer metastasis is a common biological phenomenon observed in malignant tumors that can lead to death in affected individuals [...].
Cancer metastasis is a common biological phenomenon observed in malignant tumors that can lead to death in affected individuals [...].
Topics: Humans; Neoplasms; Neoplasm Metastasis
PubMed: 37108286
DOI: 10.3390/ijms24087123 -
Nature Communications Nov 2021Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates...
Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone marrow to support their long-term propagation, but the precise location and mechanisms that mediate niche interactions are unknown. Using breast cancer as a model of solid tumour metastasis to the bone marrow, we applied large-scale quantitative three-dimensional imaging to characterise temporal changes in the bone marrow microenvironment during disease progression. We show that mouse mammary tumour cells preferentially home to a pre-existing metaphyseal domain enriched for type H vessels. Metastatic lesion outgrowth rapidly remodelled the local vasculature through extensive sprouting to establish a tumour-supportive microenvironment. The evolution of this tumour microenvironment reflects direct remodelling of the vascular endothelium through tumour-derived granulocyte-colony stimulating factor (G-CSF) in a hematopoietic cell-independent manner. Therapeutic targeting of the metastatic niche by blocking G-CSF receptor inhibited pathological blood vessel remodelling and reduced bone metastasis burden. These findings elucidate a mechanism of 'host' microenvironment hijacking by mammary tumour cells to subvert the local microvasculature to form a specialised, pro-tumorigenic niche.
Topics: Animals; Bone Marrow; Bone Neoplasms; Bone and Bones; Breast Neoplasms; Disease Progression; Granulocyte Colony-Stimulating Factor; Humans; Imaging, Three-Dimensional; Mammary Neoplasms, Animal; Mice; Neoplasm Metastasis; Neoplasms, Second Primary; Receptors, Colony-Stimulating Factor; Tumor Microenvironment
PubMed: 34836954
DOI: 10.1038/s41467-021-26556-6 -
Advances in Experimental Medicine and... 2020Metastasis is the most important biological potential of malignant tumour cells. A variety of mechanisms is involved in regulating tumour invasion and metastasis and... (Review)
Review
Metastasis is the most important biological potential of malignant tumour cells. A variety of mechanisms is involved in regulating tumour invasion and metastasis and interacts with each other, forming a large regulatory system. Autophagy plays an important role in organisms in maintaining environmental homoeostasis. A large amount of evidence has shown that autophagy is also involved in tumour development processes, including invasion and metastasis. Autophagy not only controls some biological processes in tumour cells but is also affected by the microenvironment. Therefore, the role of autophagy in tumours is far more important and complicated than previously estimated. The role of autophagy in tumour metastasis will be discussed in this chapter.
Topics: Autophagy; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 32671757
DOI: 10.1007/978-981-15-4272-5_22 -
International Journal of Molecular... May 2021Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms and is now recognized as a hallmark of... (Review)
Review
Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms and is now recognized as a hallmark of cancer and an attractive therapeutic target in cancer. In this review, we discuss recent advances in molecular mechanisms of how inflammation promotes tumorigenesis and metastasis and suppresses anti-tumor immunity in various types of solid tumors, including esophageal, gastric, colorectal, liver, and pancreatic cancer as well as hematopoietic malignancies.
Topics: Animals; Carcinogenesis; Hematologic Neoplasms; Humans; Inflammation; Neoplasm Metastasis
PubMed: 34063828
DOI: 10.3390/ijms22115421 -
Clinical and Translational Medicine Dec 2021Metastasis is the main cause of death in colorectal cancer (CRC). Circulating tumour cells (CTCs) are regarded as the precursor cells of metastasis. The CTCs, which...
BACKGROUND
Metastasis is the main cause of death in colorectal cancer (CRC). Circulating tumour cells (CTCs) are regarded as the precursor cells of metastasis. The CTCs, which underwent epithelial-mesenchymal transition (EMT), are associated with metastasis and responsible for poor prognosis. EMT cancer cells modulate endothelial permeability in the invasive front and facilitate cancer cell intravasation, resulting in CTCs-mediated distant metastasis. Exosomes derived from cancer cells are key mediators of cancer-host intercommunication. However, the mechanism by which EMT-tumour cells-derived exosomes modulate vascular permeability and promote CTCs generation has remained unclear.
METHODS
Exosomes isolation and purification were conducted by ultra-centrifugation. Exosomal miRNA was identified by sequencing followed by quantitative PCR. In vitro co-culture assay experiments were conducted to evaluate the effect of exosomal miR-27b-3p on the permeability of blood vessel endothelium. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) were performed to investigate the underlying mechanism by which miR-27b-3p is packaged into exosomes. A mouse model was established to determine the role of exosomal miR-27b-3p in blood vessel permeability modulation in vivo.
RESULTS
We found that EMT-CRC cells attenuate the blood vessel barrier by transferring miR-27b-3p to human umbilical vein endothelial cells (HUVECs) in exosomes. Mechanically, miR-27b-3p atteuated the expression of vascular endothelial cadherin (VE-Cad) and p120 at the post-transcriptional level by binding to 3'-untranslated region of VE-Cad and p120 directly. The packaging of miR-27b-3p into exosomes was induced by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which activated by STAT3. Clinically, miR-27b-3p up-regulated in CRC tissues. Plasma exosomal miR-27b-3p was positively correlated with malignant progression and CTC count in CRC patients. Our study reveals a novel mechanism by which EMT-CRC cells promote metastasis, increasing blood vessel permeability and facilitating the generation of CTCs.
CONCLUSION
Exosomal miR-27b-3p secreted by EMT-CRC cells increases blood vessel permeability and facilitates the generation of CTCs. Exosomal miR-27b-3p may become a promising biomarker for CRC metastasis.
Topics: Aged; Capillary Permeability; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Female; Humans; Male; MicroRNAs; Middle Aged; Neoplasm Metastasis; Neoplastic Cells, Circulating
PubMed: 34936736
DOI: 10.1002/ctm2.595 -
Amino Acids Dec 2021Cancer cells often change their metabolism to support uncontrolled proliferation. Proline is the only proteogenic secondary amino acid that is abundant in the body.... (Review)
Review
Cancer cells often change their metabolism to support uncontrolled proliferation. Proline is the only proteogenic secondary amino acid that is abundant in the body. Recent studies have shown that proline metabolism plays an important role in metabolic reprogramming and affects the occurrence and development of cancer. Proline metabolism is related to ATP production, protein and nucleotide synthesis, and redox homeostasis in tumor cells. Proline can be synthesized by aldehyde dehydrogenase family 18 member A1 (ALDH18A1) and delta1-pyrroline-5-carboxylate reductase (PYCR), up-regulating ALDH18A1 and PYCR can promote the proliferation and invasion of cancer cells. As the main storage of proline, collagen can influence cancer cells proliferation, invasion, and metastasis. Its synthesis depends on the hydroxylation of proline catalyzed by prolyl 4-hydroxylases (P4Hs), which will affect the plasticity and metastasis of cancer cells. The degradation of proline occurs in the mitochondria and involves an oxidation step catalyzed by proline dehydrogenase/proline oxidase (PRODH/POX). Proline catabolism has a dual role in cancer, linking apoptosis with the survival and metastasis of cancer cells. In addition, it has been demonstrated that the regulation of proline metabolic enzymes at the genetic and post-translational levels is related to cancer. This article reviews the role of proline metabolic enzymes in cancer proliferation, apoptosis, metastasis, and development. Research on proline metabolism may provide a new strategy for cancer treatment.
Topics: Animals; Apoptosis; Cell Proliferation; Humans; Neoplasm Metastasis; Neoplasms; Proline
PubMed: 34390414
DOI: 10.1007/s00726-021-03060-1 -
Cold Spring Harbor Perspectives in... Nov 2020Sterile inflammation within primary tumor tissues can spread to distant organs that are devoid of tumor cells. This happens in a manner dependent on tumor-led secretome,... (Review)
Review
Sterile inflammation within primary tumor tissues can spread to distant organs that are devoid of tumor cells. This happens in a manner dependent on tumor-led secretome, before the actual metastasis occurs. The premetastatic microenvironment is established in this way and is at least partly regulated by hijacking the host innate immune system. The biological manifestation of premetastasis include increased vascular permeability, cell mobilization via the blood stream, degradation of the extracellular matrix, immunosuppression, and host antineoplastic activities.
Topics: Animals; Humans; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 31615874
DOI: 10.1101/cshperspect.a036897 -
Cancer Letters Nov 2020Metastasis is a critical cause of treatment failure and death in patients with advanced malignancies. Tumor cells can leave the primary site and enter the bloodstream;... (Review)
Review
Metastasis is a critical cause of treatment failure and death in patients with advanced malignancies. Tumor cells can leave the primary site and enter the bloodstream; these circulating tumor cells then colonize target organs by overcoming blood shear stress, evading immune surveillance, and silencing the offensive capabilities of immune cells, eventually forming metastatic foci. From leaving the primary focus to the completion of distant metastasis, malignant tumor cells are supported and/or antagonized by certain immune cells. In particular, it has been found that myeloid granulocytes play an important role in this process. This review therefore aims to comprehensively describe the significance of neutrophils in solid tumor metastasis in terms of their supporting role in initiating the invasion and migration of tumor cells and assisting the colonization of circulating tumor cells in distant target organs, with the hope of providing insight into and ideas for anti-tumor metastasis treatment of tumor patients.
Topics: Blood Platelets; Cell Movement; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Cells, Circulating; Neutrophils
PubMed: 32745581
DOI: 10.1016/j.canlet.2020.07.028 -
Essays in Biochemistry Oct 2019In this review, we present recent findings on the dynamic nature of the tumour microenvironment (TME) and how intravital microscopy studies have defined TME components... (Review)
Review
In this review, we present recent findings on the dynamic nature of the tumour microenvironment (TME) and how intravital microscopy studies have defined TME components in a spatiotemporal manner. Intravital microscopy has shed light into the nature of the TME, revealing structural details of both tumour cells and other TME co-habitants in vivo, how these cells communicate with each other, and how they are organized in three-dimensional space to orchestrate tumour growth, invasion, dissemination and metastasis. We will review different imaging tools, imaging reporters and fate-mapping strategies that have begun to uncover the complexity of the TME in vivo.
Topics: Animals; Extracellular Matrix; Humans; Intravital Microscopy; Neoplasm Metastasis; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 31654075
DOI: 10.1042/EBC20190019 -
Cold Spring Harbor Perspectives in... May 2020Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor... (Review)
Review
Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor cells from their constraining basement membrane at the primary site, migration and intravasation into the circulation, survival in the circulation, extravasation into the secondary organ, and survival and growth at the secondary site. During these steps, tumor and immune cells interact and influence each other both within the tumor microenvironment and systemically. In particular, myeloid cells such as monocytes, macrophages, neutrophils, and myeloid-derived suppressor cells (myeloid regulatory cells) have been shown to play important roles in the metastatic process. These interactions open new avenues for targeting cancer metastasis, especially given the increasing interest in development of cancer immunotherapies. In this review, we describe the currently reported pathways and mechanisms involved in myeloid cell enhancement of the metastatic cascade.
Topics: Animals; Humans; Immunotherapy; Myeloid Cells; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 31548218
DOI: 10.1101/cshperspect.a038026