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Prevention of Melanoma Extravasation as a New Treatment Option Exemplified by p38/MK2 Inhibition

Skin & Endothelial Research Division, Department of Dermatology, Medical University Vienna, A-1090 Vienna, Austria
Int. J. Mol. Sci. 2020, 21(21), 8344; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218344
Received: 19 October 2020 / Revised: 2 November 2020 / Accepted: 2 November 2020 / Published: 6 November 2020
(This article belongs to the Special Issue Targeting MAPK in Cancer 2.0)
Melanoma releases numerous tumor cells into the circulation; however, only a very small fraction of these cells is able to establish distant metastasis. Intravascular survival of circulating tumor cells is limited through hemodynamic forces and by the lack of matrix interactions. The extravasation step is, thus, of unique importance to establish metastasis. Similar to leukocyte extravasation, this process is under the control of adhesion molecule pairs expressed on melanoma and endothelial cells, and as for leukocytes, ligands need to be adequately presented on cell surfaces. Based on melanoma plasticity, there is considerable heterogeneity even within one tumor and one patient resulting in a mixture of invasive or proliferative cells. The molecular control for this switch is still ill-defined. Recently, the balance between two kinase pathways, p38 and JNK, has been shown to determine growth characteristics of melanoma. While an active JNK pathway induces a proliferative phenotype with reduced invasive features, an active p38/MK2 pathway results in an invasive phenotype and supports the extravasation step via the expression of molecules capable of binding to endothelial integrins. Therapeutic targeting of MK2 to prevent extravasation might reduce metastatic spread. View Full-Text
Keywords: melanoma; extravasation; p38; MK2; endothelium melanoma; extravasation; p38; MK2; endothelium
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MDPI and ACS Style

Petzelbauer, P. Prevention of Melanoma Extravasation as a New Treatment Option Exemplified by p38/MK2 Inhibition. Int. J. Mol. Sci. 2020, 21, 8344. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218344

AMA Style

Petzelbauer P. Prevention of Melanoma Extravasation as a New Treatment Option Exemplified by p38/MK2 Inhibition. International Journal of Molecular Sciences. 2020; 21(21):8344. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218344

Chicago/Turabian Style

Petzelbauer, Peter. 2020. "Prevention of Melanoma Extravasation as a New Treatment Option Exemplified by p38/MK2 Inhibition" Int. J. Mol. Sci. 21, no. 21: 8344. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218344

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