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Experimental & Molecular Medicine Apr 2020Recurrent cancer that spreads to distant sites is the leading cause of disease-related death among cancer patients. Cancer cells are likely to disseminate during cancer... (Review)
Review
Recurrent cancer that spreads to distant sites is the leading cause of disease-related death among cancer patients. Cancer cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. These dormant cancer cells (DCCs) are rarely detectable with current diagnostic systems. Moreover, they can interpret homoeostatic signals from the microenvironment, thereby evading immune surveillance and chemotherapy. Eventually, DCCs can reawaken in response to signals, which are not yet fully understood, resulting in recurrence and metastasis. Therefore, understanding the biology of DCC reawakening is key to preventing metastasis. Over the last decade, a growing body of literature has revealed the mechanisms involved in cancer dormancy and reawakening. The cytotoxic activity of immune cells can cause cancer cells to enter a dormant state, and chronic inflammation can reactivate cancer proliferation at distant sites. Upon the binding of circulating DCCs to extracellular molecules, various signaling cascades are activated and reinitiate cell proliferation. In the present review, we attempt to consolidate the existing literature to provide a framework for the understanding of this crucial step in cancer progression.
Topics: Animals; Biomarkers; Cell Cycle; Energy Metabolism; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Metastasis; Neoplasms; Neoplastic Stem Cells; Signal Transduction; Tumor Microenvironment
PubMed: 32300189
DOI: 10.1038/s12276-020-0423-z -
Molecular Oncology Jan 2017The epithelial-mesenchymal transition (EMT) is a developmental program that enables stationary epithelial cells to gain the ability to migrate and invade as single... (Review)
Review
The epithelial-mesenchymal transition (EMT) is a developmental program that enables stationary epithelial cells to gain the ability to migrate and invade as single cells. Tumor cells reactivate EMT to acquire molecular alterations that enable the partial loss of epithelial features and partial gain of a mesenchymal phenotype. Our understanding of the contribution of EMT to tumor invasion, migration, and metastatic outgrowth has evolved over the past decade. In this review, we provide a summary of both historic and recent studies on the role of EMT in the metastatic cascade from various experimental systems, including cancer cell lines, genetic mouse tumor models, and clinical human breast cancer tissues.
Topics: Animals; Breast Neoplasms; Cell Movement; Disease Models, Animal; Epithelial-Mesenchymal Transition; Female; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating
PubMed: 28085222
DOI: 10.1002/1878-0261.12017 -
Biochimica Et Biophysica Acta Jan 2015MicroRNAs (miRNAs) are integral molecules in the regulation of numerous physiological cellular processes that have emerged as critical players in cancer initiation and... (Review)
Review
MicroRNAs (miRNAs) are integral molecules in the regulation of numerous physiological cellular processes that have emerged as critical players in cancer initiation and metastatic progression, both by promoting and suppressing metastasis. Recently, cell-free miRNAs shed from cancer cells into circulation have been reported in cancer patients, raising hope for development of novel biomarkers that can be routinely measured in easily accessible samples. In fact, establishing miRNA expression in the circulation likely has advantages over determination in primary tumor tissue, further augmenting the potential applications of miRNA detection in oncological practice. In addition, secretion of miRNAs impacting distant cell signaling or promoting the formation of a niche that sustains a distant tumor microenvironment allows for new treatment approaches to thwart cancer progression.
Topics: Animals; Cell-Free System; Exosomes; Humans; MicroRNAs; Molecular Targeted Therapy; Neoplasm Metastasis
PubMed: 25450578
DOI: 10.1016/j.bbcan.2014.10.005 -
Molecular Cancer Nov 2023Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor... (Review)
Review
Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process of tumor metastasis. There is no previous text that provides a comprehensive review of the role of EVs on CTCs during tumor metastasis. In this paper, we reviewed the mechanisms of EVs on CTCs during tumor metastasis, including the ability of EVs to enhance the shedding of CTCs, protect CTCs in circulation and determine the direction of CTC metastasis, thus affecting the distant metastasis of tumors.
Topics: Humans; Neoplastic Cells, Circulating; Extracellular Vesicles; Neoplasm Metastasis; Biomarkers, Tumor
PubMed: 38037077
DOI: 10.1186/s12943-023-01909-5 -
The Journal of Clinical Investigation Mar 2021The tumor microenvironment profoundly influences the behavior of recruited leukocytes and tissue-resident immune cells. These immune cells, which inherently have... (Review)
Review
The tumor microenvironment profoundly influences the behavior of recruited leukocytes and tissue-resident immune cells. These immune cells, which inherently have environmentally driven plasticity necessary for their roles in tissue homeostasis, dynamically interact with tumor cells and the tumor stroma and play critical roles in determining the course of disease. Among these immune cells, neutrophils were once considered much more static within the tumor microenvironment; however, some of these earlier assumptions were the product of the notorious difficulty in manipulating neutrophils in vitro. Technological advances that allow us to study neutrophils in context are now revealing the true roles of neutrophils in the tumor microenvironment. Here we discuss recent data generated by some of these tools and how these data might be synthesized into more elegant ways of targeting these powerful and abundant effector immune cells in the clinic.
Topics: Animals; Disease Progression; Humans; Immunotherapy; Models, Immunological; Neoplasm Metastasis; Neoplasms; Neutropenia; Neutrophils; Translational Research, Biomedical; Tumor Microenvironment
PubMed: 33720040
DOI: 10.1172/JCI143759 -
Cancer Research Sep 2020Cancer metastasis poses a challenging problem both clinically and scientifically, as the stochastic nature of metastatic lesion formation introduces complexity for both... (Review)
Review
Cancer metastasis poses a challenging problem both clinically and scientifically, as the stochastic nature of metastatic lesion formation introduces complexity for both early detection and the study of metastasis in preclinical models. Engineered metastatic niches represent an emerging approach to address this stochasticity by creating bioengineered sites where cancer can preferentially metastasize. As the engineered niche captures the earliest metastatic cells at a nonvital location, both noninvasive and biopsy-based monitoring of these sites can be performed routinely to detect metastasis early and monitor alterations in the forming metastatic niche. The engineered metastatic niche also provides a new platform technology that serves as a tunable site to molecularly dissect metastatic disease mechanisms. Ultimately, linking the engineered niches with advances in sensor development and synthetic biology can provide enabling tools for preclinical cancer models and fosters the potential to impact the future of clinical cancer care.
Topics: Animals; Bioengineering; Biopsy; Biosensing Techniques; Cell Movement; Humans; Neoplasm Metastasis; Neoplasms; Organ Specificity; Precision Medicine; Synthetic Biology; Tumor Hypoxia; Tumor Microenvironment
PubMed: 32409307
DOI: 10.1158/0008-5472.CAN-20-0079 -
Seminars in Diagnostic Pathology Jan 2023Metastasis may be the secret weapon cancer uses to dominate and subjugate, to persist and prevail. However, it is no longer a secret when we realize that a stem cell has... (Review)
Review
Metastasis may be the secret weapon cancer uses to dominate and subjugate, to persist and prevail. However, it is no longer a secret when we realize that a stem cell has the same ways and means to fulfill its own omnipotence and accomplish its own omnipresence… and when we realize that a cancer cell has its own version of stem-ness origin and stem-like nature. In this perspective, we discuss whether stem-ness enables metastasis or mutations drive metastasis. We ponder about low-grade versus high-grade tumors and about primary versus metastatic tumors. We wonder about stochasticity and hierarchy in the genesis and evolution of cancer and of metastasis. We postulate that metastasis may hold the elusive code that makes or breaks a stem-cell versus a genetic theory of cancer. We speculate that the vaunted model of multistep carcinogenesis may be in error and needs some belated remodeling and a major overhaul. We propose that subsequent malignant neoplasms from germ cell tumors and donor-derived malignancies in organ transplants are quintessential experiments of nature and by man that may eventually empower us to elucidate a stem-cell origin of cancer and metastasis. Unfortunately, even the best experiments of cancer and of metastasis will be left unfinished, overlooked, or forgotten, when we do not formulate a proper cancer theory derived from pertinent and illuminating clinical observations. Ultimately, there should be no consternations when we realize that metastasis has a stem-cell rather than a genetic origin, and no reservations when we recognize that metastasis has been providing us some of the most enduring tests and endearing proofs to demonstrate that cancer is indeed a stem-cell rather than a genetic disease after all.
Topics: Male; Humans; Neoplasms; Stem Cells; Mutation; Neoplasm Metastasis
PubMed: 35729019
DOI: 10.1053/j.semdp.2022.06.012 -
Current Osteoporosis Reports Jun 2021Bone metastasis occurs in advanced stages of breast cancer, worsening the quality of life and increasing the mortality of patients. Current treatments for bone... (Review)
Review
Bone metastasis occurs in advanced stages of breast cancer, worsening the quality of life and increasing the mortality of patients. Current treatments for bone metastasis are only palliative, and efficient therapeutic targets need to be still identified. MicroRNAs (miRNAs) are a large class of small non-coding RNAs that regulate gene expression within cells. Interestingly, the expression of certain miRNAs has been associated with several stages of bone metastasis progression, highlighting the importance of these small RNAs during the course of the metastatic disease. In this review, we aim to summarise the most recent findings on miRNAs and their mRNA targets in driving breast cancer bone metastasis. Furthermore, we discuss the possibility to use miRNAs as direct therapeutic targets or as advanced therapies for breast cancer bone metastasis, as well as their potential as predictive biomarkers of bone metastasis for an early diagnosis and a better tailoring of therapies for cancer patients.
Topics: Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Female; Humans; MicroRNAs; Molecular Targeted Therapy; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 33830428
DOI: 10.1007/s11914-021-00677-9 -
Frontiers in Bioscience (Elite Edition) Jan 2011The spread of cancer cells in the body -'metastasis,' is a challenging issue for cancer patients and for cancer research. From a clinical point of view, the majority of... (Review)
Review
The spread of cancer cells in the body -'metastasis,' is a challenging issue for cancer patients and for cancer research. From a clinical point of view, the majority of the cancer-related deaths in patients who suffer from solid cancers are metastasis-related. Although this life threatening consequence in cancer is recognised almost immediately at the time of diagnosis, the current-state-of-knowledge on the mechanisms and effective ways to combat cancer metastasis in clinical settings is far from being realized. Thus, making the necessity of continuing research into cancer metastasis evermore demanding and critical. This issue of the journal is directed toward consideration of some of the salient aspects of cancer metastasis, with a focus on recent progress of the molecular and cellular mechanisms of cancer invasion and metastasis.
Topics: Cell Adhesion; Cell Movement; Extracellular Matrix; Humans; Intercellular Signaling Peptides and Proteins; Neoplasm Invasiveness; Neoplasm Metastasis; Neovascularization, Pathologic
PubMed: 21196319
DOI: 10.2741/e254 -
Molecular Oncology Jan 2017
Topics: Animals; Epithelial-Mesenchymal Transition; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating
PubMed: 28085221
DOI: 10.1002/1878-0261.12024