Breaking the blood-brain barrier is at least one of the causes of death in cancer animals

The goal of most cancer treatments is to eliminate or at least prevent the growth of malignant cells
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A study published in the journal Developmental Cell on September 7 pointed out a possible complementary strategy: strengthening the host’s defenses, especially the blood-brain barrier (BBB)

This work " shows that (breaking) the blood-brain barrier is at least one of the causes of death in cancer animals, " said Wu-Min Deng, who studies fruit fly tumors at Tulane University School of Medicine.
He was not involved in this.
Studies
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He added: "This is a good example of how the fruit fly model can be used to answer some very difficult questions in cancer biology

Over the past two decades, David Bilder's team at the University of California, Berkeley has used fruit fly models to better understand cancer
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Then, "About eight or nine years ago, a very good student came to the laboratory.

In 2015, this student named Alejandra Figueroa-Clarevega (Alejandra Figueroa-Clarevega) and Bilder discovered in fruit flies that malignant tumors produce a protein that disrupts insulin signaling.
Causes the so-called cachexia, that is, the breakdown of fat and muscle, leading to a rapid weight loss, which is related to the death of many human cancer patients
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This research inspired Jung Kim, a postdoctoral fellow in Bilder's lab, who led this new study, using fruit flies to explore other ways tumors affect hosts in distant parts of the body

Kim, Bilder, and colleagues began transplanting tissues expressing the activating oncogenes Ras and aPKC into wild-type adults, where the tissues formed malignant, non-metastatic tumors
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These tumors killed these animals within a few weeks-about half the life span of fruit flies that received non-cancerous tissue transplants

The blood-brain barrier of fruit flies is composed of glial, which protects the brain from the open circulation of hemolymph (circulating fluid of fruit flies)
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Researchers check whether the blood-brain barrier is intact by injecting a dye into the hemolymph

Next, the research team knocked out the Drosophila interleukin 6 (IL-6) homologous gene, which is a cytokine that can activate JAK/STAT signaling
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A receptor that binds to IL-6 homologs; or self-regulates in the graft or host tissue

The effect of preserving the blood-brain barrier of fruit flies is "very significant"
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They live longer in the presence of tumors," Bilder said

The cytokines released by the tumor cause cell connections that usually protect the brain from circulating molecules, as shown in the picture, which trace the diffusion of dyes
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In order to explore whether the interaction between tumors and the blood-brain barrier is conserved in vertebrates, his team worked with collaborators at Berkeley who have expertise in mice with melanoma-derived tumors
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They also found that cancer caused a breakdown of the IL-6-dependent blood-brain barrier
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When IL-6 signaling was blocked, the mice's condition alleviated
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Julia Cordero, a cancer biologist at the University of Glasgow in Scotland who was not involved in the study, wrote in an email to The Scientist that mouse research Put forward the "exciting possibility that the mechanism found in fruit flies may be related to human diseases
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She added that the experiment to evaluate the blood-brain barrier in a mouse model developed into a tissue-specific tumor-which is an extension of the work of injecting melanoma cells, as the author has done here-"is likely to be this A follow-up to a groundbreaking fruit fly study
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” Bilder explained that they chose the mouse model because tumors have been shown to up-regulate cytokines related to fruit flies, so it’s not clear whether this finding can be used in other types of cancer.
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At the same time, he said, “Many cancers are known to cause severe systemic inflammation, so we certainly hope that it can inspire clinicians who do not observe the blood-brain barrier of patients” to do so
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This study is "a clever way to think about the blood-brain barrier," said Natasha O'Brown, who studied the zebrafish blood-brain barrier at Harvard Medical School but was not involved in this work
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An open question is: "If you induce a tumor and then remove the tumor, will the decomposition still exist?" She added that many signaling pathways start and strengthen themselves, so knowing how much damage after tumor resection is reversible may be similar to humans.
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Understanding the specific factors that lead to death after the blood-brain barrier is damaged is Bilder's top priority
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"This may be something that the tumor produces in the circulation and then enters the brain to harm it," he said, "but we can't rule out that it has gone the other way"-that is, a factor that leaves the brain is causing death Reason
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Author: Abby Olena

Original search: Tumor-induced disruption of the blood-brain barrier promotes host death