CancerStemCellNicheWords
--Sacking the Cancer Stem Cell Neighborhood--
[This article was posted on "Science Magazine's" website today, to coincide with the embargoed release of a paper from "Cancer Cell."]
Scientists have found the Achilles heel of a special class of cells that jump starts tumor growth. According to a new study, targeting the niche where they live is the key to destroying these previously invincible cells. This insight paves the way for more effective cancer therapy.
Until recently, researchers believed that all cells in a tumor were pretty much the same. But in the early 1990s, a team at the University of Toronto found some interesting characters hanging out in a population of leukemia cells: instead of rapidly dividing like their companions, about one in every million leukemia cells was capable of maintaining itself in a culture dish without differentiating and then initiating tumor growth when transplanted. These were indications that the cell was likely a stem cell.
Since then, researchers have discovered similar stem cells—including those behind acute myeloma leukemia, two brain cancers, and breast cancer—but no drug to date has successfully eliminated CSCs, which infinitely renew themselves and generate cells to replenish the tumor even after the bulk of it has been eliminated by chemotherapy or radiation. CSCs can do this in part because they grow at a sluggish rate, rendering them insensitive to conventional therapies designed to target rapidly dividing cells.
Now, researchers lead by neurobiologist Richard Gilbertson at St. Jude Children's Research Hospital in Memphis, Tennessee, have found a way to target cancer stem cells independently from the bulk of the tumor. They did so by looking for similarities between these stem cells and non-cancerous neural stem cells. Neural stem cells—immature cell masses that give rise to more specialized cells that form nerve tissue—are concentrated in blood vessel-rich regions called "vascular niches." These regions are lined with endothelial cells, which secrete chemical signals that promote stem cell survival. Gilbertson's team inferred that cancer stem cells might require a similar niche.
Sure enough, after examining a large cohort of human brain tumors, the researchers found that cancer stem cells were frequently located close to capillaries—the body's tiniest blood vessels. When the researchers injected human brain tumor cells called medulloblastomas together with endothelial cells in mice, the animals sprouted larger tumors than mice receiving tumor cells alone, the team reports today in Cancer Cell. This experiment further supports the role of endothelial cells and the vascular niche in providing signals that promote tumor growth.
Additionally, in tumor-bearing mice, drugs used to deplete blood vessels caused a significant drop in CSCs and subsequently inhibited tumor growth. The same vessel-killing drugs hardly effected the survival of cells in rest of the tumor, confirming that CSCs require a vascular niche.
"This study is an excellent example of bringing stem cell insight to cancer," says Richard Wechsler-Reya, a cancer biologist at Duke University Medical Center in Durham, North Carolina. "I think this is going to be the beginning of a really popular approach to treating cancer stem cells."
.MGW.
[This article was posted on "Science Magazine's" website today, to coincide with the embargoed release of a paper from "Cancer Cell."]
Scientists have found the Achilles heel of a special class of cells that jump starts tumor growth. According to a new study, targeting the niche where they live is the key to destroying these previously invincible cells. This insight paves the way for more effective cancer therapy.
Until recently, researchers believed that all cells in a tumor were pretty much the same. But in the early 1990s, a team at the University of Toronto found some interesting characters hanging out in a population of leukemia cells: instead of rapidly dividing like their companions, about one in every million leukemia cells was capable of maintaining itself in a culture dish without differentiating and then initiating tumor growth when transplanted. These were indications that the cell was likely a stem cell.
Since then, researchers have discovered similar stem cells—including those behind acute myeloma leukemia, two brain cancers, and breast cancer—but no drug to date has successfully eliminated CSCs, which infinitely renew themselves and generate cells to replenish the tumor even after the bulk of it has been eliminated by chemotherapy or radiation. CSCs can do this in part because they grow at a sluggish rate, rendering them insensitive to conventional therapies designed to target rapidly dividing cells.
Now, researchers lead by neurobiologist Richard Gilbertson at St. Jude Children's Research Hospital in Memphis, Tennessee, have found a way to target cancer stem cells independently from the bulk of the tumor. They did so by looking for similarities between these stem cells and non-cancerous neural stem cells. Neural stem cells—immature cell masses that give rise to more specialized cells that form nerve tissue—are concentrated in blood vessel-rich regions called "vascular niches." These regions are lined with endothelial cells, which secrete chemical signals that promote stem cell survival. Gilbertson's team inferred that cancer stem cells might require a similar niche.
Sure enough, after examining a large cohort of human brain tumors, the researchers found that cancer stem cells were frequently located close to capillaries—the body's tiniest blood vessels. When the researchers injected human brain tumor cells called medulloblastomas together with endothelial cells in mice, the animals sprouted larger tumors than mice receiving tumor cells alone, the team reports today in Cancer Cell. This experiment further supports the role of endothelial cells and the vascular niche in providing signals that promote tumor growth.
Additionally, in tumor-bearing mice, drugs used to deplete blood vessels caused a significant drop in CSCs and subsequently inhibited tumor growth. The same vessel-killing drugs hardly effected the survival of cells in rest of the tumor, confirming that CSCs require a vascular niche.
"This study is an excellent example of bringing stem cell insight to cancer," says Richard Wechsler-Reya, a cancer biologist at Duke University Medical Center in Durham, North Carolina. "I think this is going to be the beginning of a really popular approach to treating cancer stem cells."
.MGW.
posted by Meagan G at
2:02 PM
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