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

08:00 EDT 13th August 2019 | BioPortfolio

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

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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This article was published in the following journal.

Name: Cell reports
ISSN: 2211-1247
Pages: 1785-1798.e6

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Medical and Biotech [MESH] Definitions

A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.

The directional growth of an organism in response to an external stimulus such as light, touch, or gravity. Growth towards the stimulus is a positive tropism; growth away from the stimulus is a negative tropism. (From Concise Dictionary of Biology, 1990)

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Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.

A cellular subtype of malignant melanoma. It is a pigmented lesion composed of melanocytes occurring on sun-exposed skin, usually the face and neck. The melanocytes are commonly multinucleated with a "starburst" appearance. It is considered by many to be the in situ phase of lentigo maligna melanoma.

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