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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.
This article was published in the following journal.
Name: Cell reports
Chronic activation of glial cells contributes to neurodegenerative diseases. Cytochrome c (CytC) is a soluble mitochondrial protein that can act as a damage-associated molecular pattern (DAMP) when re...
During acute lung injury, lung fibroblasts produce chemokines that assist the activation and migration of resident macrophages. The interactions between pulmonary fibroblasts and alveolar macrophages ...
Dysfunctional regulation of inflammation may contribute to the progression of neurodegenerative diseases. The results of this study revealed that DJ-1, a Parkinson's disease (PD) gene, regulated expre...
The major cause of melanoma mortality is metastasis to distant organs, including lungs and brain. Reciprocal interactions of metastasizing tumor cells with stromal cells in secondary sites play a crit...
Accumulating evidence has shown that astrocytes play a critical role in neuroinflammation and protection against oxidative stress. In this study, we investigated the effects of sigma-1 receptor (Sig-1...
The impact of the postoperative inflammatory response on the central nervous system after cardiac surgery is uncertain. The goal of this study was to evaluate the role of complement activ...
Up to 50% of patients with unresectable metastatic melanoma will develop brain metastases during their lifetime. A possible treatment options for patients with brain metastases are surgery...
This is a Phase II-III multi-center prospective randomized controlled clinical trial of incident adult renal transplant patients. The primary objective of this study is to determine if th...
This open-label, single-arm, multicenter study will evaluate the efficacy and safety in patients with metastatic melanoma who developed brain metastases. Patients may or may not have recei...
This research is being done because melanoma in the brain is very difficult to treat because it does not respond to radiation or to chemotherapy, such as temozolomide. One of the reasons f...
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)
An unpigmented malignant melanoma. It is an anaplastic melanoma consisting of cells derived from melanoblasts but not forming melanin. (Dorland, 27th ed; Stedman, 25th ed)
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.
Melanoma is a highly malignant tumor of melanin-forming cells (melanocytes) There are most commonly found in the skin (resulting from sunlight exposure), but also in the eyes and mucous membranes. Metastasis to other regions of the body is also common....
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Basal cell carcinoma Basal cell carcinoma, or BCC, is a cancer of the basal cells at the bottom of the epidermis. It’s very common ...
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