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Apoptosis is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 billion cells each day due to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells.
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.
In humans, clusterin (CLU) is encoded by the CLU gene on chromosome 8. CLU is an extracellular molecular chaperone which binds to misfolded proteins in body fluids to neutralise their toxicity and mediate their cellular uptake by receptor-mediated endocytosis. Once internalised by cells, complexes between CLU and misfolded proteins are trafficked to lysosomes where they are degraded. CLU is involved in many diseases including neurodegenerative diseases, cancers, inflammatory diseases, and aging.
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.
P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.
Intravasation is the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel. Intravasation is one of several carcinogenic events that initiate the escape of cancerous cells from their primary sites. Other mechanisms include invasion through basement membranes, extravasation, and colonization of distant metastatic sites. Cancer cell chemotaxis also relies on this migratory behavior to arrive at a secondary destination designated for cancer cell colonization.
Interleukin 33 (IL-33) is a protein that in humans is encoded by the IL33 gene.
Maspin is a protein that in humans is encoded by the SERPINB5 gene. This protein belongs to the serpin superfamily. SERPINB5 was originally reported to function as a tumor suppressor gene in epithelial cells, suppressing the ability of cancer cells to invade and metastasize to other tissues. Furthermore, and consistent with an important biological function, Maspin knockout mice were reported to be non-viable, dying in early embryogenesis. However, a subsequent study using viral transduction as a method of gene transfer was not able to reproduce the original findings and found no role for maspin in tumour biology. Furthermore, the latter study demonstrated that maspin knockout mice are viable and display no obvious phenotype. These data are consistent with the observation that maspin is not expressed in early embryogenesis. The precise molecular function of maspin is thus currently unknown.
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2.
Matrilysin also known as matrix metalloproteinase-7 (MMP-7), pump-1 protease (PUMP-1), or uterine metalloproteinase is an enzyme in humans that is encoded by the MMP7 gene. The enzyme has also been known as matrin, putative metalloproteinase-1, matrix metalloproteinase pump 1, PUMP-1 proteinase, PUMP, metalloproteinase pump-1, putative metalloproteinase, MMP). Human MMP-7 has a molecular weight around 30 kDa.
Leukotriene B4 receptor 2, also known as BLT2, BLT2 receptor, and BLTR2, is an Integral membrane protein that is encoded by the LTB4R2 gene in humans and the Ltbr2 gene in mice.
RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.
WNT1-inducible-signaling pathway protein 1 (WISP-1), is a member of the CCN protein family and should correctly be referred to as CCN4 as suggested by the International CCN Society. It is a matricellular protein that in humans is encoded by the WISP1 gene.
Invadopodia are actin-rich protrusions of the plasma membrane that are associated with degradation of the extracellular matrix in cancer invasiveness and metastasis. Very similar to podosomes, invadopodia are found in invasive cancer cells and are important for their ability to invade through the extracellular matrix, especially in cancer cell extravasation. Invadopodia are generally visualized by the holes they create in ECM -coated plates, in combination with immunohistochemistry for the invadopodia localizing proteins such as cortactin, actin, Tks5 etc. Invadopodia can also be used as a marker to quantify the invasiveness of cancer cell lines in vitro using a hyaluronic acid hydrogel assay.
A macrophage-activating factor (MAF) is a lymphokine or other receptor based signal that primes macrophages towards cytotoxicity to tumors, cytokine secretion, or clearance of pathogens. Similar molecules may cause development of an inhibitory, regulatory phenotype. A MAF can also alter the ability of macrophages to present MHC I antigen, participate in Th responses, and/or affect other immune responses.
Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV.
The hallmarks of cancer were originally six biological capabilities acquired during the multistep development of human tumors and have since been increased to eight capabilities and two enabling capabilities. The idea was coined by Douglas Hanahan and Robert Weinberg in their paper "The Hallmarks of Cancer" published January 2000 in Cell.
The tumor microenvironment is a complex ecosystem surrounding a tumor, composed of cancer cells, stromal tissue and the extracellular matrix. Mutual interaction between cancer cells and the different components of the tumor microenvironment support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. The tumor microenvironment is in constant change because of the tumor's ability to 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.
Invasion is the process by which cancer cells directly extend and penetrate into neighboring tissues in cancer. It is generally distinguished from metastasis, which is the spread of cancer cells through the circulatory system or the lymphatic system to more distant locations. Yet, lymphovascular invasion is generally the first step of metastasis.
References
- ↑ Frisch SM, Screaton RA (October 2001). "Anoikis mechanisms". Current Opinion in Cell Biology. 13 (5): 555–62. doi:10.1016/S0955-0674(00)00251-9. PMID 11544023.
- ↑ Frisch, SM.; Francis, H. (Feb 1994). "Disruption of epithelial cell-matrix interactions induces apoptosis". J Cell Biol. 124 (4): 619–26. doi:10.1083/jcb.124.4.619. PMC 2119917 . PMID 8106557.
- ↑ Mawji IA, Simpson CD, Gronda M, et al. (September 2007). "A chemical screen identifies anisomycin as an anoikis sensitizer that functions by decreasing FLIP protein synthesis". Cancer Research. 67 (17): 8307–15. doi: 10.1158/0008-5472.CAN-07-1687 . PMID 17804746.
- ↑ Mawji IA, Simpson CD, Hurren R, et al. (May 2007). "Critical role for Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein in anoikis resistance and distant tumor formation". Journal of the National Cancer Institute. 99 (10): 811–22. doi: 10.1093/jnci/djk182 . PMID 17505076.
- ↑ Paoli P, Giannoni E, Chiarugi P (2013). "Anoikis molecular pathways and its role in cancer progression". Biochim Biophys Acta. 1833 (12): 3481–3498. doi: 10.1016/j.bbamcr.2013.06.026 . PMID 23830918.