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Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term stromal comes from Latin stromat-, "bed covering", and Ancient Greek στρῶμα, strôma, "bed".
Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.
Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.
The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.
Brachyury is a protein that, in humans, is encoded by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra.
Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).
Carcinosarcomas are malignant tumors that consist of a mixture of carcinoma and sarcoma. Carcinosarcomas are rare tumors, and can arise in diverse organs, such as the skin, salivary glands, lungs, the esophagus, pancreas, colon, uterus and ovaries.
Tyrosine-protein kinase receptor UFO is an enzyme that in humans is encoded by the AXL gene. The gene was initially designated as UFO, in allusion to the unidentified function of this protein. However, in the years since its discovery, research into AXL's expression profile and mechanism has made it an increasingly attractive target, especially for cancer therapeutics. In recent years, AXL has emerged as a key facilitator of immune escape and drug-resistance by cancer cells, leading to aggressive and metastatic cancers.
Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the SNAI2 gene. It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation.
Periostin is a protein that in humans is encoded by the POSTN gene. Periostin functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 integrins to support adhesion and migration of epithelial cells.
A mesenchymal–epithelial transition (MET) is a reversible biological process that involves the transition from motile, multipolar or spindle-shaped mesenchymal cells to planar arrays of polarized cells called epithelia. MET is the reverse process of epithelial–mesenchymal transition (EMT) and it has been shown to occur in normal development, induced pluripotent stem cell reprogramming, cancer metastasis and wound healing.
Adult mesenchymal stem cells are being used by researchers in the fields of regenerative medicine and tissue engineering to artificially reconstruct human tissue which has been previously damaged. Mesenchymal stem cells are able to differentiate, or mature from a less specialized cell to a more specialized cell type, to replace damaged tissues in various organs.
Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.
The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.
A cancer-associated fibroblast (CAF) is a cell type within the tumor microenvironment that promotes tumorigenic features by initiating the remodelling of the extracellular matrix or by secreting cytokines. CAFs are a complex and abundant cell type within the tumour microenvironment; the number cannot decrease, as they are unable to undergo apoptosis.
Breast cancer is the most prevalent type of cancer among women globally, with 685,000 deaths recorded worldwide in 2020. The most commonly used treatment methods for breast cancer include surgery, radiotherapy and chemotherapy. Some of these treated patients experience disease relapse and metastasis. The aggressive progression and recurrence of this disease has been attributed the presence of a subset of tumor cells known as breast cancer stem cells (BCSCs). These cells possess the abilities of self-renewal and tumor initiation, allowing them to be drivers of metastases and tumor growth. The microenvironment in which these cells reside is filled with residential inflammatory cells that provide the needed signaling cues for BCSC-mediated self-renewal and survival. The production of cytokines allows these cells to escape from the primary tumor and travel through the circulation to distant organs, commencing the process of metastasis. Due to their significant role in driving disease progression, BCSCs represent a new target by which to treat the tumor at the source of metastasis.
Cédric Blanpain is a Belgian researcher in the field of stem cells. He is a tenured professor of developmental biology and genetics at Université Libre de Bruxelles and director of the stem cell and cancer lab at its Faculty of Medicine. He was one of the first researchers in the world to use cell lineage tracing in cancer research and he showed for the first time the existence of cancer stem cells in solid tumors in vivo. He was selected by Nature as one of 10 People who mattered most in 2012 and he received the outstanding young investigator award of the International Society for Stem Cell Research.
Shimon Slavin, M.D., is an Israeli professor of medicine. Slavin pioneered the use of immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation for the cure of hematological malignancies and solid tumors, and using hematopoietic stem cells for induction of transplantation tolerance to bone marrow and donor allografts.
References
- 1 2 Sell, Stewart. (2004). "Stem cell origin of cancer and differentiation therapy". Critical Reviews in Oncology/Hematology. 51 (1): 1–28. doi:10.1016/j.critrevonc.2004.04.007. PMID 15207251.
- ↑ Nowak, D.; Stewart, D.; Koeffler, H. P. (2009). "Differentiation therapy of leukemia: 3 decades of development". Blood. 113 (16): 3655–65. doi:10.1182/blood-2009-01-198911. PMC 2943835 . PMID 19221035.
- ↑ Leszczyniecka, M; Roberts, T; Dent, P; Grant, S; Fisher, P. B. (2001). "Differentiation therapy of human cancer: Basic science and clinical applications". Pharmacology & Therapeutics. 90 (2–3): 105–56. doi:10.1016/s0163-7258(01)00132-2. PMID 11578655.
- ↑ Pattabiraman, D. R.; Bierie, B.; Kober, K. I.; Thiru, P.; Krall, J. A.; Zill, C.; Reinhardt, F.; Tam, W. L.; Weinberg, R. A. (2016). "Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability". Science. 351 (6277): aad3680. doi:10.1126/science.aad3680. PMC 5131720 . PMID 26941323.
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