Introduction
Cell motility is currently one of the “hottest” areas in biology. An example of normal healthy migration is in adult skin, when cells migrate from the inner tissue to the outer layer to form a protective coating of dead skin cells. However, when referring to tumors, cell migration is dangerous. Skin tumors arise in the epidermis. The tumor then invades the dermis, creating a metastatic lesion, which breaks down tissue, including bone.
This paper experiments with the two forms of morphology, elongated and rounded. The elongated morphology is dependent on Rac, a signaling protein. When GDP binds to the Rac, the signal is off and when GTP binds, it is turned on. The rounded morphology is dependent on a signal from Rho and ROCK, two more signaling proteins. Rho only sends a signal to move when it is activated by GTP. When protease activity is inhibited, elongated cells convert to the rounded form, and continue migration. So, to inhibit the movement of tumor cells, it is necessary to stop the elongated and rounded morphology.
This experiment used Y27632, which inhibits Rho and PI, a protease which inhibits Rac. Through the use of these two inhibitors, Sahai and Marshall attempt to determine what exactly is most effective in preventing tumor movement and which signaling proteins activate which morphology.
Methods
I.) Distinct Modes of motility have different requirements for Rho and ROCK activity
a. Methods
1.
BE (colon carcinoma), LS174T (colon carcinoma), SW962 (squamous cell carcinoma), WM266.4 (melanoma), A375P, and A375m2(melanoma) cells were analyzed to test for cell invasion relative to the controls used.
2.
The two controls used were TAT-C3 (which inactivates the RhoA, Rho...
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...the elongated cells would not accomplish much.
Tumor cells can also change the shape of movement that they use, so these inhibitors that stop the signaling in the cells may not be as effective as hoped. Though they would stop the rounded cells, the cells might be able to switch to an elongated shape and continue in their migration to other areas of the tissues. There are other methods, though, that would cause elongated cells to switch to the rounded cell shape for their migration. Sahai and Marshall are hoping that with further research, these two treatments may be combined to stop the migration of the cancerous cells and be a realistic, useable treatment for cancer in the future.
Works Cited
Erik Sahai and Christopher J. Marshall - "Differeing modes of tumour cell invations have distinct requirements for Rho/ROCK signalling and extracellular proteolysis."
...ozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111-5.
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