Bio422 Takehome questions. Pleasenote that References for your sources need to be included in the answers.
1. Find a gene that is either up-regulated ordown-regulated in either Intravasation or Extravasation and explain how itsregulation affects that process. (4)Cyclooxygenase-2,or COX2, promotes extravasationin the lung (Bos 2009). COX2 has been researched and found to enable “extravasationof breast cancer cells across the blood-brain barrier” (Lee 2011). In order for this occur, COX2is induced from human brain endothelial cells, and this plays a crucial role inthe transmigration (Lee 2011). Furthermore, COX2 expression in primarytumors enhances cancer cells for extravasation through the “non-fenestrated” capillariesof the brain and lungs. In addition, the up-regulationof COX2, which is involved in both the “vascular and extracellular matrixremodeling,” promotes extravasation and metastasis (Labelle 2012).
Overall,COX2 plays a role in up-regulation in extravasation when dealing with the lungsand the brain. References:Bos PD, ZhangXH, Nadal C, Shu W, Gomis RR, Nguyen DX, MinnAJ, van de Vijver MJ, Gerald WL, Foekens JA, Massagué J.(2009).
“Genes that mediate breast cancer metastasis to the brain.” Nature, 459(7249):1005-9. doi:10.1038/nature08021. Epub 2009 May 6.Labelle, M., &Hynes, R.
O. (2012). “The initial hours of metastasis: the importance ofcooperative host-tumor cell interactions during hematogenous dissemination.
” CancerDiscovery, 2(12), 1091–1099.http://doi.org/10.1158/2159-8290.
CD-12-0329LeeKY, Kim YJ, Yoo H, Lee SH, Park JB, Kim HJ. (2011).Human brain endothelial cell-derived COX-2 facilitates extravasation of breastcancer cells across the blood-brain barrier. Anticancer Res, 31(12):4307-13.
2. Please discuss the structure and functions ofICAM-1 and MUC-1. (4) ICAM-1, or Intercellular AdhesionMolecule 1, is known as a protein-coding gene that encodes a cell surfaceglycoprotein.
ICAM-1 can bind to integrins “CD11a / CD18 or CD11b / CD18,” andcan be manipulated by “Rhinovirus as a receptor” (ICAM1 2017). For ICAM-1’s structure, it is an “immunoglobulin-like protein”that is expressed in soluble form and is capable of being membrane-bound to thesurface of endothelial cells and cells used in the immune response (Pietruczuk 2014). In addition, ICAM-1 plays a vital role in the “adhesionand migration of leukocytes to the sites of inflammation” (Pietruczuk2014). MUC-1, or Mucin 1, is also a protein-codinggene that encodes a membrane-bound protein. Mucins are known to be “O-glycosylatedproteins” that aid in the formation of protective mucous barriers found onepithelial surfaces (MUC1 2017). MUC1 is a “large, trans-membrane mucinglycoprotein” that is expressed at the “apical surface” and will line themucosal surfaces of many different tissues that include lung, breast stomachand pancreas (Brayman 2004). What these proteins do is play a role inintracellular signaling and are typically used as “a diagnostic marker formetastatic progression” (Horm 2013).
When looking at ICAM-1 and MUC-1together, it has been studied that the MUC1 peptide core facilitates firm adhesion of tumorcells to adjacent cells from binding to ICAM-1. From research, there isincreasing evidence that MUC-1 is involved in signaling. ICAM-1 is currentlythe only known direct ligand of the MUC1 extracellular domain (Rhan 2009). References: Brayman, M.,Thathiah, A., Carson, D. D. (2004).
MUC1: A multifunctional cell surfacecomponent of reproductive tissue epithelia. Reproductive Biology andEndocrinology?: RB, 2, 4.http://doi.org/10.1186/1477-7827-2-4HormTM, Schroeder JA. (2013). (2013). “MUC1 and metastatic cancer: expression,function and therapeutic targeting.
” CellAdh Migr, 7(2):187-98. doi: 10.4161/cam.23131.ICAM1Gene(Protein Coding). (n.d.).
Retrieved December 03, 2017, fromhttp://www.genecards.org/cgi-bin/carddisp.
pl?gene=ICAM1MUC1Gene(Protein Coding). (n.d.). Retrieved December 03, 2017, from http://www.genecards.org/cgi-bin/carddisp.
pl?gene=MUC1=MUC-1PietruczukM, Pietruczuk A, Pancewicz S, Hermanowska-Szpakowicz T. (2014).”ICAM-1: structure, biological role and clinical significance.” Pol Merkur Lekarski, 17(101): 507-11.RahnJJ, Shen Q, Mah BK, Hugh JC. (2009). “MUC1 Initiates aCalcium Signal after Ligation by Intercellular Adhesion Molecule-1.
” J. Biol. Chem, 279: 29386-.