Stories about: metastasis

Curbing metastasis in lung cancer by taking a cue from the nervous system

What's drawing lung cancer cells to migrate? (Juan Gaertner/Shutterstock)
What’s drawing lung cancer cells to migrate? (Juan Gaertner/Shutterstock)

Ninety percent of lung cancer deaths are caused by the tumor’s spread—or metastasis—to other organs. Researchers have now discovered an approach to blocking metastasis in the most common type of lung cancer, adenocarcinoma, that potentially could be added to chemotherapy treatments aimed at shrinking the primary tumor.

Kerstin Sinkevicius, PhD, a research fellow at Boston Children’s Hospital, started with this question: Is there anything in a lung tumor’s environment that makes it metastasize? She sampled tissue from human lymph nodes—the first place cancers typically spread to—to see if the cells there were secreting anything that might lure cancer cells to migrate.

One chemical stood out: a growth factor called brain-derived neurotrophic factor, or BDNF. Secreted near maturing neurons, BDNF is best known for its role in stimulating the developing nervous system.

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Turning tumors against themselves to stop metastasis

Tumor cells need the right environment in order to spread. But a protein that some tumors themselves produce can make some environments inhospitable to metastasis. (Albh/Wikimedia Commons)
With cancer, it’s generally not the primary tumor that kills people, but metastasis—the spread of cancer to locations far from the original tumor.

Finding ways of stopping metastasis has proven immensely challenging. On some level, it’s a problem with the models that we use to study metastatic cancer. But it’s also a matter of understanding why particular tumor types spread where they do—like prostate tumors to the bones or breast cancer to the brain—and what about the microenvironment—the combination of cells, proteins and other factors—makes different sites in the body metastatically friendly to different tumors.

Randolph Watnick, PhD, and his research team in Boston Children’s Vascular Biology Program have been asking this question, and in the process have found that a protein called prosaposin can make sites unfriendly to metastasis. Interestingly, it’s a protein that some tumors actually make themselves.

But even better, Watnick has found that a tiny fragment of prosaposin—a peptide that is a mere five amino acids long—has the same anti-metastatic power of the full protein, making it highly attractive for drug development. He and his collaborators reported the full story in a recent paper in the journal Cancer Discovery.

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The problem with modeling metastatic cancers: Is it the mouse’s fault?

While the mouse is widely used to model many diseases, including cancer, the results we gain from it rarely translate well to people. But whose fault is it? (Wednesday Elf - Mountainside Crochet/Flickr)

The humble house mouse (or Mus musculus) is probably the most widely used model animal in biomedical research (beating out my favorite, the zebrafish, by a long mile). Millions are studied around the world every year, helping us understand the genetics of health and disease as well as the biology of cancer, diabetes and a host of other conditions. Mouse modeling is also often a major step in developing and getting FDA approval for new drugs.

But the mouse sometimes gets a bad rap in the research world. While it can be an effective and affordable model, and 95 percent of its genes are similar to ours, it is less than ideal for some of the diseases we study with it.

Take cancer, for instance. It’s relatively easy to cure cancer in a mouse; we’ve done it millions of times over. (The late Judah Folkman, MD, founding father of Boston Children’s Hospital’s Vascular Biology Program (VBP) and of the field of angiogenic research, famously said, “If you’re a mouse and you have cancer, we can take good care of you.”) Mouse and human tumor cells are fundamentally different in many ways. And the way that tumors behave in mouse models doesn’t necessarily reflect the way they behave in their natural environment (that is, in us)—a major consideration, especially when it comes to looking for new treatments for cancer that has spread (aka metastasized). More often than not, drugs that are successful in mouse models fail in the clinic.

But is it the mouse’s fault? Or is the problem the way we develop our models and run our experiments?

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The cell from hell: Can we outsmart cancer stem cells?

Cancer stem cells’ clever defenses may be the seeds of their undoing. (Image: leftover bacon/OpenClipArt)

Some scientists still debate the existence of cancer stem cells – rare cells that can singlehandedly perpetuate a tumor, and possibly make it more aggressive.  But others have moved on, isolating candidate cancer stem cells and documenting their distinctive characteristics and markers.

And some are starting to figure out how these cells operate and leverage that knowledge to come up with new approaches to cancer therapy.

Children’s scientist Markus Frank has been building quite a dossier on cancer stem cells, starting with melanoma stem cells. “Many of the features that make a cancer bad seem to be localized in this subpopulation of cells,” he says.

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Angiogenesis inhibition and metastasis: The saga continues

If you were a cancer patient receiving anti-angiogenic therapy, and you heard media reports that this treatment might make you worse and not better, what would you do? Recent peer-reviewed studies have indicated that inhibitors of vascular endothelial growth factor (VEGF), the central factor controlling formation of new blood vessels, actually promote tumor invasiveness and increase metastasis in animal models – far from their intended effect of forcing the cancer into remission. Vector covered this surprising twist last fall. Understandably, as these findings got out, some patients called their physicians and asked to be taken off the drugs.

Knowing all this, I was eager to attend this week’s World Anti-Angiogenesis Summit, which promised a panel discussion addressing the controversy. It’s one that interests me, as I am the licensing manager for the Vascular Biology Program at Children’s Hospital Boston.

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