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Glossary
Circulating Tumor Cell (CTC)
CTCs are thought to originate from the primary tumor from which they escape and colonize new tissues which they reach by traveling in the blood stream. They are believed to be the cause of metastasis. Therefore, they can be used as an early marker for metastatic cancer [Cáceres, 2015]. CTCs can be detected in the blood before the formation of metastasis, therefore allowing early intervention. However, CTCs are very scarce and detection methods have to be accordingly sensitive.
Warburg Effect
Malignant tumors often tune their metabolism towards highly elevated rates of glycolysis, followed by lactic acid fermentation, rather than pyruvate hydrolysis in mitochondria. This gives the tumor cells a comparative advantage over normal cells due to the rapid intake of glucose for which the cells are competing. This effect is referred to as the Warburg effect since it was first described by Otto Warburg. It is not clear what the ultimate cause of this effect is. The transition to lactic acid fermentation occurs also in environments plenty of oxygen, and once it occurred, tumor cells keep this feature even in transition to metastasis [Vander Heiden et al, 2009].
Figure 5. Warburg effect scheme. Image from Vander Heiden, 2009
TRAIL
The Tumor Necrosis Factor Related Apoptosis Inducing Ligand, TRAIL, is an important protein of our immune system which induces apoptosis in cells expressing the required death receptors, DR4 and DR5, thereby inactivating the target cell. Binding of TRAIL to DR4 or DR5 on the surface of a target cell leads to Caspase-8 dependent induction of apoptosis. Cancer cells often express elevated levels of the DR4 and DR5 death receptors and are therefore especially susceptible to treatment with TRAIL, whereas healthy cells are generally not harmed by TRAIL. In nature, TRAIL exists as a membrane-bound and a soluble version. In our system we are using the soluble form, referred to as sTRAIL [Johnstone, 2008].
Quorum sensing
Quorum sensing is a system by which bacteria "sense each other". This cell to cell communication is mediated by chemical signals such as AHL. This is a means to tune gene expression depending on the density of the population [Miller, 2001].
Epithelial-mesenchymal transition
The Epithelial-mesenchymal tenasition (EMT) takes place when epithelial cells detach from the wall of blood or lymphatic vessels and enter the circulatory system. These cells develop into multipotent stromal cells during normal embryonal development. However, a similar process occurs when cancerous cells invade the circulatory system to spread all over the body [Kalluri, 2009].
LldP
L-lactate permease which partcipates in the active transport of Lactate, D-lactate and glycolate by using a proton force.
LldR
L-lactate regulator which controls the expression of the LldPRD operon in E. coli. In the absence of L-lactate gene expression is blocked by the transcription regulator. When L-lactate is present it binds to LldR and gene expression is activated.