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Molecular Cancer Feb 2011Many hypotheses have been postulated to explain the intricate nature of the metastatic process, but none of them completely accounted for the actual biological and... (Review)
Review
Many hypotheses have been postulated to explain the intricate nature of the metastatic process, but none of them completely accounted for the actual biological and clinical observations. Consequently, metastasis still remains an open issue with only few metastasis-inducing proteins experimentally validated so far. Recently proposed novel metastatic model, where serial and parallel metastatic processes are adequately integrated, might help to bridge the current gap between experimental results and clinical observations. In addition, the identification, isolation and molecular characterization of cancer stem cells, a population of the cells within the tumour mass able to proliferate, self-renew and induce tumorigenesis, will shed new light on the complex molecular events mediating metastasis, invasion and resistance to therapy. Understanding the molecular basis of these tumour characteristics will usher in a new age of individualized cancer therapy. In this review article, we will provide a current overview of molecular mechanisms underpinning metastasis, and discuss recent findings in this field obtained by global molecular profiling strategies such as proteomics.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Models, Biological; Neoplasm Metastasis; Proteomics; Tropism
PubMed: 21342498
DOI: 10.1186/1476-4598-10-22 -
Anti-cancer Drugs Jul 2004In the past decade, research from various disciplines has stimulated a re-evaluation of our ideas of how cancers metastasize. Two important findings have been... (Review)
Review
In the past decade, research from various disciplines has stimulated a re-evaluation of our ideas of how cancers metastasize. Two important findings have been fundamental to this re-evaluation: that cancer cells are subject to growth regulation at the secondary site and that a specific class of proteins suppresses the metastatic phenotype. These proteins are encoded by metastasis suppressor genes, which are operationally defined as genes that suppress in vivo metastasis without inhibiting primary tumor growth when transfected into metastatic cell lines and injected into experimental animals. Recent biochemical studies have shown that certain metastasis suppressor proteins participate in highly conserved signal transduction cascades that mediate cellular responses to growth factors, cytokines and cellular stresses. Further elucidation of the biochemical foundations of these pathways coupled with strong in vivo studies should give us insight into the mechanisms of cancer metastasis, and may hold important implications for the future of cancer staging and therapy, using both existing and novel modalities.
Topics: Animals; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Neoplasm Metastasis; Receptor Cross-Talk; Signal Transduction
PubMed: 15205597
DOI: 10.1097/01.cad.0000132233.36512.fa -
International Anesthesiology Clinics 2016
Review
Topics: Humans; Neoplasm Metastasis; Neoplasm Seeding; Neoplasms; Neoplastic Cells, Circulating; Neovascularization, Pathologic; Perioperative Period
PubMed: 27648889
DOI: 10.1097/AIA.0000000000000124 -
Breast DiseaseMost solid tumors contain hypoxic regions. Hypoxia affects a variety of tumor cell properties such as cell growth rate, neovascularization, metastasis and sensitivity to... (Review)
Review
Most solid tumors contain hypoxic regions. Hypoxia affects a variety of tumor cell properties such as cell growth rate, neovascularization, metastasis and sensitivity to treatment. Breast 3cancer is the second most common cause of death in women. Nearly half of breast cancer patients treated for localized disease develop metastases and often combinations of local and systemic therapy are not curative. Tissue oxygenation measurements in human breast carcinomas have shown large areas of hypoxic tissue and immunolocalized signals of the hypoxic markers, CAIX and HIF-1 alpha, in breast cancer tissue show strong staining around necrotic regions. A wide range of genes associated with breast cancer metastasis have been reported to be upregulated under hypoxic conditions and hypoxic gene signatures are associated with poorer outcome in breast cancer. An understanding of the molecular pathways in hypoxia-induced breast cancer metastasis promises potential useful prognostic and therapeutic information.
Topics: Breast Neoplasms; Cell Hypoxia; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Metastasis
PubMed: 17473365
DOI: 10.3233/bd-2007-26105 -
Cancer Metastasis Reviews Mar 2008The possibility of predicting clinical outcome of cancer patients through the analysis of gene expression profiles in the primary tumor is a kind of ideological... (Review)
Review
The possibility of predicting clinical outcome of cancer patients through the analysis of gene expression profiles in the primary tumor is a kind of ideological revolution as the multistep carcinogenesis model postulates that the proportion of cells within the primary tumor that actually acquire metastasis driving mutation(s) is small; too small to leave its imprint on the gene expression profile. The data collected to date have brought a new paradigm to reality in the metastasis field: metastasis must at least in part rely on mutations and/or gene regulation events present in the majority of cells which constitute the primary tumor mass. By analyses of differential expression of primary tumors versus metastases or by functional analyses of putative metastasis genes in experimental metastasis, many metastasis-associated gene expression events have been identified that correlate with the development of metastases. Among genes "favoring" metastasis, we find many molecules that are expressed not by the tumor cell itself but by the cells of the microenvironment, as well as genes over-expressed in the primary tumor that have a principle role in mediating tumor-host interactions. Here we review these concepts and advance hypotheses on how gene expression of the primary tumor and the microenvironment can favor the spread of the metastasis seeds and how this knowledge can provide tools to secondary prevention.
Topics: Gene Expression; Genes, Neoplasm; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 18046511
DOI: 10.1007/s10555-007-9111-x -
Cancer Treatment and Research 2007
Review
Topics: Animals; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Stem Cells; Neovascularization, Pathologic
PubMed: 17953412
DOI: 10.1007/978-0-387-69219-7_9 -
World Journal of Urology 1996The molecular basis of tumorigenesis and metastasis has been under intense analysis over the last few years. Tumor progression is a multistep process involving the... (Review)
Review
The molecular basis of tumorigenesis and metastasis has been under intense analysis over the last few years. Tumor progression is a multistep process involving the interplay of several molecules. Initiated by spontaneous mutations, cellular alterations occur, which may result in a metastatic phenotype. The transition from a nonmalignant to a malignant cell is governed by mechanisms similar to those implicated in normal cellular differentiation and development. Epithelial cells might lose their polarity and adhesive contacts to become invasive carcinoma cells. Such a complex transformation has been summarized in the term epithelial-mesenchymal transition (EMT). In the analysis of tumor progression it is of particular interest that metastasis-specific gene products are involved in embryonic development and, furthermore, play a role in blood cell migration, tissue remodeling, and wound healing during adulthood. Herein we present a synopsis of the newest developments in molecular biology with respect to tumorigenesis and metastasis in the light of specific molecules involved in EMT.
Topics: Animals; Disease Progression; Embryo, Mammalian; Humans; Neoplasm Metastasis; Neoplasms; Proteins
PubMed: 8806192
DOI: 10.1007/BF00186893 -
Current Pharmaceutical Biotechnology Nov 2011The metastatic cascade and colonization remains a major challenge in clinical therapeutics. The formation of metastasis has many rate limiting steps. The expression of... (Review)
Review
The metastatic cascade and colonization remains a major challenge in clinical therapeutics. The formation of metastasis has many rate limiting steps. The expression of metastases initiation genes in primary tumors is driven by the need for cell motility, invasiveness, handling the shear stress in the vasculature and lymphatic circulation, and the survival and persistent growth in the distant organ. However, the expression of the progression genes in the primary tumors has a more complex basis. These metastasis-prone genes support primary tumor growth through one particular effect, whereas they enhance distant metastasis through another effect. The boundaries between metastasis initiation and metastasis progression genes are not rigid. In this review, we examine novel gene signatures identified in metastases, address key inflammatory factors mastering homing selection, gain further mechanistic insights into cell plasticity and evaluate the role of microRNAs. Moreover, we also describe the recent progress in developing nanoparticle imaging substantiating a promising theranostic platform for future cancer diagnostics and treatment, and assess the relevance of the bioinformatic analysis of metastasis-related proteins with an eye toward the metastatic niche. All these tools will provide valuable biological information of the progression of the disease, helping find potential therapeutic targets and improving surgical procedures. In a near future the understanding of the molecular mechanisms in tumor dissemination will be pivotal for the translation of these methods to the clinic and will help to overcome the barriers in clinical therapy of metastases.
Topics: Animals; Disease Progression; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Neoplasm Invasiveness; Neoplasm Metastasis; Signal Transduction
PubMed: 21470130
DOI: 10.2174/138920111798376996 -
Virchows Archiv : An International... Jun 2009Malignant tumors invade and metastasize. They consist of cancer cells, evolving through genetic and epigenetic modulation, mixed with tumor-associated host cells,... (Review)
Review
Malignant tumors invade and metastasize. They consist of cancer cells, evolving through genetic and epigenetic modulation, mixed with tumor-associated host cells, emerging from resident or bone marrow-derived precursors. These cells establish ecosystems to activate cellular programs for local invasion and distant metastasis. Characteristic of such malignancy-related activities is communication inside ecosystems between cells, ligands, receptor protein complexes, and signaling pathways as well as between ecosystems comprising the primary tumor, lymph node and distant metastasis, bone marrow and blood and lymph circulation. Complexity is another characteristic, resulting from: heterogeneity of the cell populations; the numbers of promoter and suppressor genes, their levels of regulation, and the pleiotropic activities of their products; biological redundancy of the molecular mechanisms underpinning invasion-related activities. Clinical attention is paid to putative new targets, namely host cells, individual molecules and their signaling pathways, as well as the effects of current treatment on invasion and metastasis.
Topics: Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Signal Transduction
PubMed: 19471961
DOI: 10.1007/s00428-009-0784-0 -
Nature Reviews. Cancer Nov 2020Metastatic dissemination occurs very early in the malignant progression of a cancer but the clinical manifestation of metastases often takes years. In recent decades,... (Review)
Review
Metastatic dissemination occurs very early in the malignant progression of a cancer but the clinical manifestation of metastases often takes years. In recent decades, 5-year survival of patients with many solid cancers has increased due to earlier detection, local disease control and adjuvant therapies. As a consequence, we are confronted with an increase in late relapses as more antiproliferative cancer therapies prolong disease courses, raising questions about how cancer cells survive, evolve or stop growing and finally expand during periods of clinical latency. I argue here that the understanding of early metastasis formation, particularly of the currently invisible phase of metastatic colonization, will be essential for the next stage in adjuvant therapy development that reliably prevents metachronous metastasis.
Topics: Disease Progression; Humans; Neoplasm Metastasis; Neoplasms; Neoplasms, Second Primary; Neoplastic Processes
PubMed: 33024261
DOI: 10.1038/s41568-020-00300-6