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Metastasis as an evolutionary process

Michael Bordonaro
Virulence is defined as the ability of a pathogen to cause morbidity and/or mortality in infected hosts. The relationship between virulence and transmissibility is complex; natural selection may promote decreased virulence to enhance host mobility and increase the probability for transmission, or transmissibility may be enhanced by increased virulence, leading to higher pathogen load and, in some cases, superior evasion from host defenses. An evolutionary trade-off exists between the ability of pathogens to maintain opportunities for long-term transmission via suppressed virulence and increased short-term transmission via enhanced virulence...
2018: Journal of Cancer
Altea Targa, Giulia Rancati
Pioneering studies described cancer as an evolutionary process and detailed its intratumor heterogeneity in patients' specimens. The development of unbiased single-cell sequencing technologies confirmed these early observations and neoplasms are now widely recognized as populations of genetically, chromosomally and epigenetically distinct cells in which clones carrying beneficial traits expand in presence of selection factors like chemotherapy treatment. In support of this view, intratumor heterogeneity, by providing a large pool of phenotypically distinct clones, was shown to correlate with poor prognosis, therapy failure and metastasis...
June 2018: Current Opinion in Cell Biology
Marta Bertolaso, Anna Maria Dieli
The major transitions approach in evolutionary biology has shown that the intercellular cooperation that characterizes multicellular organisms would never have emerged without some kind of multilevel selection. Relying on this view, the Evolutionary Somatic view of cancer considers cancer as a breakdown of intercellular cooperation and as a loss of the balance between selection processes that take place at different levels of organization (particularly single cell and individual organism). This seems an elegant unifying framework for healthy organism, carcinogenesis, tumour proliferation, metastasis and other phenomena such as ageing...
October 2017: Royal Society Open Science
Nicola Gaianigo, Davide Melisi, Carmine Carbone
Pancreatic cancer (PC) is the third leading cause of adult cancer mortality in the United States. The poor prognosis for patients with PC is mainly due to its aggressive course, the limited efficacy of active systemic treatments, and a metastatic behavior, demonstrated throughout the evolution of the disease. On average, 80% of patients with PC are diagnosed with metastatic disease, and the half of those who undergo surgery and adjuvant therapy develop liver metastasis within two years. Metastatic dissemination is an early event in PC and is mainly attributed to an evolutionary biological process called epithelial-to-mesenchymal transition (EMT)...
September 12, 2017: Cancers
Claudia Peitzsch, Anna Tyutyunnykova, Klaus Pantel, Anna Dubrovska
Metastatic tumors are the cause of more than 90% of cancer related deaths. Metastasis formation can be considered as a culmination of the Darwinian evolutionary process within the tumor, when competition of multiple clones results in the development of cell inherent traits that favor tumor dissemination. Cancer stem cells (CSC) which possess self-renewal properties and genomic instability are considered to be an engine of tumor evolution. Cancer cells which have the capacity to colonize distant organs have the features of CSC and, in addition, exert their tumor-initiating capacity under adverse microenvironmental conditions...
June 2017: Seminars in Cancer Biology
Jonas Demeulemeester, Parveen Kumar, Elen K Møller, Silje Nord, David C Wedge, April Peterson, Randi R Mathiesen, Renathe Fjelldal, Masoud Zamani Esteki, Koen Theunis, Elia Fernandez Gallardo, A Jason Grundstad, Elin Borgen, Lars O Baumbusch, Anne-Lise Børresen-Dale, Kevin P White, Vessela N Kristensen, Peter Van Loo, Thierry Voet, Bjørn Naume
BACKGROUND: Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. RESULTS: We sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients...
December 9, 2016: Genome Biology
Dan Høgdall, Colm J O'Rourke, Andrzej Taranta, Douglas V N P Oliveira, Jesper B Andersen
Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current clinical strategies and patient outcome...
2016: Digestive Diseases
Samra Turajlic, Charles Swanton
Therapeutic advances in oncology have not fully translated to the treatment of metastatic disease, which remains largely incurable. Metastatic subclones can emerge both early and late in the life of the primary tumor. A better understanding of the genetic evolution of metastatic disease has the potential to reveal differences in the therapeutic vulnerabilities of primary and metastatic tumors, shed light on the temporal patterns of and routes to metastatic colonization, and provide insight into the biology of the metastatic process...
April 8, 2016: Science
Masoud Zeinali, Armin Adelinik, Shaghayegh Papian, Hossein Khorramdelazad, Mehdi Abedinzadeh
Galectins constitute an evolutionary conserved family that binds to β-galactosides. There is growing evidence that galectins are implicated in essential biological processes such as cellular communication, inflammation, differentiation and apoptosis. Galectin-3 is one of the best-known galectins, which is found in vertebrates. Galectin-3 has been shown to be expressed in some cell lines and plays important roles in several physiological and pathological processes, including cell adhesion, cell activation and chemoattraction, cell cycle, apoptosis, cell growth, and differentiation...
October 2015: Human Immunology
Mark C Lloyd, Katarzyna A Rejniak, Joel S Brown, Robert A Gatenby, Emily S Minor, Marilyn M Bui
A major goal of modern medicine is increasing patient specificity so that the right treatment is administered to the right patient at the right time with the right dose. While current cancer studies have largely focused on identification of genetic or epigenetic properties of tumor cells, emerging evidence has clearly demonstrated substantial genetic heterogeneity between tumors in the same patient and within subclones of a single tumor. Thus, molecular analysis from populations of cells (either a whole tumor or small biopsy of that tumor) is, at best, an incomplete representation of the underlying biology...
July 2015: Advances in Anatomic Pathology
E N M Nolte-'t Hoen, E Van Rooij, M Bushell, C-Y Zhang, R H Dashwood, W P T James, C Harris, D Baltimore
MicroRNAs (miRNAs) are one of a growing class of noncoding RNAs that are involved in the regulation of a wide range of metabolic processes including cellular differentiation, cell proliferation and apoptosis. The generation of miRNA is regulated in complex ways, for example by small interfering RNAs (small nucleolar and nuclear RNAs) and various other metabolites. This complexity of control is likely to explain how a relatively small part of the DNA that codes for proteins has enabled the evolution of such complex organisms as mammals...
August 2015: Journal of Internal Medicine
Gunes Gundem, Peter Van Loo, Barbara Kremeyer, Ludmil B Alexandrov, Jose M C Tubio, Elli Papaemmanuil, Daniel S Brewer, Heini M L Kallio, Gunilla Högnäs, Matti Annala, Kati Kivinummi, Victoria Goody, Calli Latimer, Sarah O'Meara, Kevin J Dawson, William Isaacs, Michael R Emmert-Buck, Matti Nykter, Christopher Foster, Zsofia Kote-Jarai, Douglas Easton, Hayley C Whitaker, David E Neal, Colin S Cooper, Rosalind A Eeles, Tapio Visakorpi, Peter J Campbell, Ultan McDermott, David C Wedge, G Steven Bova
Cancers emerge from an ongoing Darwinian evolutionary process, often leading to multiple competing subclones within a single primary tumour. This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths. However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported, recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and interclonal cooperation between multiple subclones...
April 16, 2015: Nature
Chao Liu, Chi Zhang, Jing Su, Dongsheng Zhang, Sha Cao
"Cancer Bioinformatics" is a new book published in 2014 by Springer. This 14-chapter book offers a quite unique and potentially controversial view about what drives a cancer to initiate, progress, metastasize and develop in an accelerated manner in metastatic sites. The book treats cancer as an evolutionary process of a diseased tissue (rather than cells) in an increasingly more challenging microenvironment; and discusses the various stresses encountered by a neoplastic tissue and their roles in (driving) cancer initiation, progression, metastasis and post-metastatic development...
April 2015: Journal of Bioinformatics and Computational Biology
Johan Vad-Nielsen, Anders Lade Nielsen
Heterochromatin protein 1α (HP1α) encoded from the CBX5-gene is an evolutionary conserved protein that binds histone H3 di- or tri-methylated at position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an essential role in forming higher order chromatin structures. HP1α has diverse functions in heterochromatin formation, gene regulation, and mitotic progression, and forms complex networks of gene, RNA, and protein interactions. Emerging evidence has shown that HP1α serves a unique biological role in breast cancer related processes and in particular for epigenetic control mechanisms involved in aberrant cell proliferation and metastasis...
2015: Cancer Biology & Therapy
Mohammad Imran Khan, Abid Hamid, Vaqar Mustafa Adhami, Rahul K Lall, Hasan Mukhtar
Globally, the cancer associated deaths are generally attributed to the spread of cancerous cells or their features to the nearby or distant secondary organs by a process known as metastasis. Among other factors, the metastatic dissemination of cancer cells is attributed to the reactivation of an evolutionary conserved developmental program known as epithelial to mesenchymal transition (EMT). During EMT, fully differentiated epithelial cells undergo a series of dramatic changes in their morphology, along with loss of cell to cell contact and matrix remodeling into less differentiated and invasive mesenchymal cells...
2015: Current Pharmaceutical Design
Matthias Voss, Ulrike Künzel, Fabian Higel, Peer-Hendrik Kuhn, Alessio Colombo, Akio Fukumori, Martina Haug-Kröper, Bärbel Klier, Gudula Grammer, Andreas Seidl, Bernd Schröder, Reinhard Obst, Harald Steiner, Stefan F Lichtenthaler, Christian Haass, Regina Fluhrer
Protein N-glycosylation is involved in a variety of physiological and pathophysiological processes such as autoimmunity, tumour progression and metastasis. Signal peptide peptidase-like 3 (SPPL3) is an intramembrane-cleaving aspartyl protease of the GxGD type. Its physiological function, however, has remained enigmatic, since presently no physiological substrates have been identified. We demonstrate that SPPL3 alters the pattern of cellular N-glycosylation by triggering the proteolytic release of active site-containing ectodomains of glycosidases and glycosyltransferases such as N-acetylglucosaminyltransferase V, β-1,3 N-acetylglucosaminyltransferase 1 and β-1,4 galactosyltransferase 1...
December 17, 2014: EMBO Journal
Jesper B Andersen
Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop with no apparent etiological background. The impact of the stromal compartment on tumor progression as well as resistance to therapy is in vogue, and the epithelial-stromal crosstalk may present a target for novel treatment strategies...
February 2015: Journal of Hepato-biliary-pancreatic Sciences
Ulrike Leppert, Andreas Eisenreich
Tissue Factor (TF) is an evolutionary conserved glycoprotein, which is of immense importance for a variety of biologic processes. TF is expressed in two naturally occurring protein isoforms, membrane-bound "full-length" (fl)TF and soluble alternatively spliced (as)TF. The TF isoform expression is differentially modulated on post-transcriptional level via regulatory factors, such as serine/arginine-rich (SR) proteins, SR protein kinases and micro (mi)RNAs. Both isoforms mediate a variety of physiologic- and pathophysiologic-relevant functions, such as thrombogenicity, angiogenesis, cell signaling, tumor cell proliferation and metastasis...
August 1, 2015: International Journal of Cancer. Journal International du Cancer
Sven Diederichs
Evolutionary conservation is widely used as an indicator of the functional significance of newly discovered genes. Although the simple search for homology at the nucleotide or amino acid sequence level has proven to be valuable for protein-coding genes, these criteria are too narrow to describe fully the selection process for long noncoding RNAs (lncRNAs). LncRNA conservation includes four dimensions: the sequence, structure, function, and expression from syntenic loci. Two recently described knockout mouse models for the lincRNAs metastasis associated lung adenocarcinoma transcript 1 (Malat1) and HOX antisense intergenic RNA (Hotair) highlight the multifaceted levels of conservation...
April 2014: Trends in Genetics: TIG
Annamaria Brioli, Lorenzo Melchor, Michele Cavo, Gareth J Morgan
It is clear that cancers comprise a mixture of clones, a feature termed intra-clonal heterogeneity, that compete for spatial and nutritional resources in a fashion that leads to disease progression and therapy resistance. This process of competition resembles the schema proposed by Darwin to explain the origin of the species, and applying these evolutionary biology concepts to cancer has the potential to improve our treatment strategies. Multiple myeloma (MM) has a unique set of characteristics that makes it a perfect model in which to study the presence of intra-clonal heterogeneity and its impact on therapy...
May 2014: British Journal of Haematology
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