Tuesday, May 13, 2014

WHAT METASTASIS TEACHES US

One can imagine what happens in the process of Metastasis as followed.   A cell with malignant transformation has acquired genetic structures that will allow it to detach from the main tumor tumor and throw itself in an unfamiliar environment, and swim in a lymphatic liquid or blood until it will find an appropriate location, and seed the place whether the local cell like it or not.   To accomplish these functions, the Metastatic cell comes prepared!  And the preparation comes with genetic Mutations, activation and depression that could be detectable by a careful non biased observer.   Each step that is outlined above and that the metastatic cell is undergoing though this process, will be affected by the natural type of the cell involved in the Metastasis.   ie, if the cell is a T lymphocyte, tissue invasion in the seeding process will use many catalytic enzymes that will breakdown the skin and other tissue environments (laminin, and other supportive molecule).  This will result in the observation of what we describe as Leukemia Cutis!   The point is that after seeding has occurred, local survival must be ensured, and it is so ensured by paracrine selective secretion of growth hormone (Mostly TGF-B as demonstrated by many types of cancers)

Going back and breaking down the process
1.cellular detachment: which will involve among othes genes the E-Cadherins
2.Movement of the cell, which will involve many processes, from genes involved in podocyte formation to protein movements inside the cell,
3.eluding autoimmune mechanisms to escape self destruction and recognition
4. adopting "mesodermal" conformation
5.swimming or displacing self along endothelial cells,
6.crossing vascular endothelium at site of seeding
7.Again avoiding detection from other cells (by providing overwhelming credentials!)
and winning the preferential nutrition game!
although most of the functions are concommitently acquired and accomplished (particularly through "embryonal" transformation or stem cell state or capability adoption), most functions are newly acquired through the neoplastic transformation (new CBF or gene binding ie BCR-Abl).

Suffice is to stress that to do these processes, the cell has to be sure it does not trigger Apoptosis and condemn itself to dying!   So unless RAS /MEK/ERK is a driver pathway, many times it has to be shut down may be through the p66shc!   This damn p66shc has been shown to help the neoplastic cell survive Anoikis.
wiki:"programmed cell death which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix (ECM)".   The point is that the cell will make sure it has plenty of Bcl-XL,   Cyclin B1,NPM1 to move forward into the Metastatic state (of course p53, Rho are involved)
CRBCM, let's go to work
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