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A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the site of the exchange of many substances from the surrounding interstitial fluid, and they convey blood from the smallest branches of the arteries (arterioles) to those of the veins (venules). Other substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in microcirculation.
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.
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.
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue.
Pericytes are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood capillaries, where they communicate with endothelial cells by means of both direct physical contact and paracrine signaling. The morphology, distribution, density and molecular fingerprints of pericytes vary between organs and vascular beds. Pericytes help to maintain homeostatic and hemostatic functions in the brain, one of the organs with higher pericyte coverage, and also sustain the blood–brain barrier. These cells are also a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. Pericytes have been postulated to regulate capillary blood flow and the clearance and phagocytosis of cellular debris in vitro. Pericytes stabilize and monitor the maturation of endothelial cells by means of direct communication between the cell membrane as well as through paracrine signaling. A deficiency of pericytes in the central nervous system can cause increased permeability of the blood–brain barrier.
Vascular endothelial growth factor, originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis and angiogenesis.
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.
Endostatin is a naturally occurring, 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin.
Thrombospondin 1, abbreviated as THBS1, is a protein that in humans is encoded by the THBS1 gene.
Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene.
Sphingosine-1-phosphate receptor 1, also known as endothelial differentiation gene 1 (EDG1) is a protein that in humans is encoded by the S1PR1 gene. S1PR1 is a G-protein-coupled receptor which binds the bioactive signaling molecule sphingosine 1-phosphate (S1P). S1PR1 belongs to a sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). S1PR1 was originally identified as an abundant transcript in endothelial cells and it has an important role in regulating endothelial cell cytoskeletal structure, migration, capillary-like network formation and vascular maturation. In addition, S1PR1 signaling is important in the regulation of lymphocyte maturation, migration and trafficking.
EGF, latrophilin and seven transmembrane domain-containing protein 1 is a latrophilin-like orphan receptor of the adhesion G protein-coupled receptor family. In humans this protein is encoded by the ELTD1 gene. ELTD1 appears to have a role in angiogenesis, both physiological and pathological in cancer.
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.
Anthrax toxin receptor 1 is a protein that in humans is encoded by the ANTXR1 gene. Its molecular weight is predicted as about 63kDa.
Sialin, also known as H(+)/nitrate cotransporter and H(+)/sialic acid cotransporter, is a protein which in humans is encoded by the SLC17A5 gene.
Vascular endothelial growth factor A (VEGF-A) is a protein that in humans is encoded by the VEGFA gene.
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.
In molecular biology mir-126 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several pre- and post-transcription mechanisms.
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.
Vasculogenic mimicry (VM) is a strategy used by tumors to ensure sufficient blood supply is brought to its cells through establishing new tumor vascularization. This process is similar to tumor angiogenesis; on the other hand vascular mimicry is unique in that this process occurs independent of endothelial cells. Vasculature is instead developed de novo by cancer cells, which under stress conditions such as hypoxia, express similar properties to stem cells, capable of differentiating to mimic the function of endothelial cells and form vasculature-like structures. The ability of tumors to develop and harness nearby vasculature is considered one of the hallmarks of cancer disease development and is thought to be closely linked to tumor invasion and metastasis. Vascular mimicry has been observed predominantly in aggressive and metastatic cancers and has been associated with negative tumor characteristics such as increased metastasis, increased tissue invasion, and overall poor outcomes for patient survival. Vascular mimicry poses a serious problem for current therapeutic strategies due to its ability to function in the presence of Anti-angiogenic therapeutic agents. In fact, such therapeutics have been found to actually drive VM formation in tumors, causing more aggressive and difficult to treat tumors to develop.
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- ↑ Yan HP, Carter CE, Wang EZ, Page DL, Washington K, Wamil BD, Yakes FM, Thurman GB, Hellerqvist CG (1998). "Functional studies on the anti-pathoangiogenic properties of CM101". Angiogenesis. 2 (3): 219–233. doi:10.1023/A:1009258801899. PMID 14517462. S2CID 21230380.
- ↑ DeVore RF, Hellerqvist CG, Wakefield GB, Wamil BD, Thurman GB, Minton PA, Sundell HW, Yan HP, Carter CE, Wang YF, York GE, Zhang MH, Johnson DH (1997). "A phase I study of the antineovascularization drug CM101". J. Clin. Cancer Res. 3 (3): 365–372. PMID 9815693.
- ↑ Nanney LB, Wamil BD, Whitsitt J, Cardwell NL, Davidson JM, Yan HP, Hellerqvist CG (2001). "CM101 Stimulates Cutaneous Wound Healing Through an Anti-Angiogenic Mechanism". Angiogenesis. 4 (1): 61–70. doi:10.1023/A:1016752925761. PMID 11824380. S2CID 25436212.
- ↑ Thurman, GB; Russell, BA; York, GE; Wang, Y-F; Page, DL; Sundell, HW; Hellerqvist, CG (1994). "Effects of GBS toxin on long-term survival of mice bearing transplanted Madison lung tumors". J. Cancer Res. Clin. Oncol. 120 (8): 479–484. doi:10.1007/BF01191801. PMID 8207046. S2CID 1257221.
- ↑ "Homo sapiens chromosome 6 genomic contig, GRCh37.p13 Primary Assembly". 2013-08-13.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ "Entrez Gene: SLC17A5 solute carrier family 17 (anion/sugar transporter), member 5"
- ↑ Haataja L, Schleutker J, Laine AP, Renlund M, Savontaus ML, Dib C, Weissenbach J, Peltonen L, Aula P (1994). "The genetic locus for free sialic acid storage disease maps to the long arm of chromosome 6". American Journal of Human Genetics. 54 (6): 1042–49. PMC 1918202 . PMID 8198127.
- ↑ Verheijen FW, Verbeek E, Aula N, Beerens CE, Havelaar AC, Joosse M, Peltonen L, Aula P, Galjaard H, van der Spek PJ, Mancini GM (1999). "A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases". Nature Genetics. 23 (4): 462–65. doi:10.1038/70585. PMID 10581036. S2CID 5709302.
- ↑ Prolo LM, Vogel H, Reimer RJ (2009). "The lysosomal sialic acid transporter sialin is required for normal CNS myelination". J. Neurosci. 29 (49): 15355–15365. doi:10.1523/JNEUROSCI.3005-09.2009. PMC 2820501 . PMID 20007460.
- ↑ Wamil BD, Thurman GB, Sundell HW, DeVore RF, Wakefield G, Johnson DH, Wang YF, Hellerqvist CG (1997). "Soluble E-selectin in cancer patients as a marker of the therapeutic efficacy of CM101, a tumor-inhibiting anti-neovascularization agent, evaluated in phase I clinical trial". J. Cancer Res. Clin. Oncol. 123 (3): 173–79. doi:10.1007/BF01214670 (inactive 2024-04-26). PMID 9119883. S2CID 30926947.
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