Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis | Zendy

Hila Doron | Zendy; Malak Amer | Zendy; Nour Ershaid | Zendy; Raquel Blazquez | Zendy; Ophir Shani | Zendy; Tzlil Gener Lahav | Zendy; Noam Cohen | Zendy; Omer Adler | Zendy; Zahi Hakim | Zendy; Sabina Pozzi | Zendy; Anna Scomparin | Zendy; Jonathan Cohen | Zendy; Muhammad Yassin | Zendy; Lea Monteran | Zendy; Rachel Grossman | Zendy; Galia Tsarfaty | Zendy; Chen Luxenburg | Zendy; Ronit SatchiFainaro | Zendy; Tobias Pukrop | Zendy; Neta Erez | Zendy

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Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis

Author(s) -

Hila Doron,

Malak Amer,

Nour Ershaid,

Raquel Blazquez,

Ophir Shani,

Tzlil Gener Lahav,

Noam Cohen,

Omer Adler,

Zahi Hakim,

Sabina Pozzi,

Anna Scomparin,

Jonathan Cohen,

Muhammad Yassin,

Lea Monteran,

Rachel Grossman,

Galia Tsarfaty,

Chen Luxenburg,

Ronit SatchiFainaro,

Tobias Pukrop,

Neta Erez

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.07.033

Subject(s) - melanoma , cxcr3 , cancer research , brain metastasis , metastasis , tropism , astrocyte , cxcl10 , medicine , downregulation and upregulation , tumor microenvironment , biology , cancer , pathology , chemokine , chemokine receptor , central nervous system , immunology , receptor , tumor cells , biochemistry , virus , gene

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.

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