Doron, Hila and Amer, Malak and Ershaid, Nour and Blazquez, Raquel and Shani, Ophir and Lahav, Tzlil Gener and Cohen, Noam and Adler, Omer and Hakim, Zahi and Pozzi, Sabina and Scomparin, Anna and Cohen, Jonathan and Yassin, Muhammad and Monteran, Lea and Grossman, Rachel and Tsarfaty, Galia and Luxenburg, Chen and Satchi-Fainaro, Ronit and Pukrop, Tobias and Erez, Neta (2019) Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis. CELL REPORTS, 28 (7). 1785-+. ISSN 2211-1247,
Full text not available from this repository. (Request a copy)Abstract
Melanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain. Brain metastases are incurable; therefore, understanding melanoma brain metastasis is of great clinical importance. We used a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanomas with the brain microenvironment. We find that CXCL10 is upregulated in metastasis-associated astrocytes in mice and humans and is functionally important for the chemoattraction of melanoma cells. Moreover, CXCR3, the receptor for CXCL10, is upregulated in brain-tropic melanoma cells. Targeting melanoma expression of CXCR3 by nanoparticle-mediated siRNA delivery or by shRNA transduction inhibits melanoma cell migration and attenuates brain metastasis in vivo. These findings suggest that the instigation of pro-inflammatory signaling in astrocytes is hijacked by brain-metastasizing tumor cells to promote their metastatic capacity and that the CXCL10-CXCR3 axis may be a potential therapeutic target for the prevention of melanoma brain metastasis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-KILLER-CELLS; METASTASIS; EXPRESSION; CHEMOKINE; POLY(ALPHA)GLUTAMATE; TRAFFICKING; PROGRESSION; DEFICIENCY; LANDSCAPE; MIGRATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 04:41 |
| Last Modified: | 01 Apr 2020 04:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26434 |
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