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cancer metastasis

Tackling Cancer Metastasis with Engineered Blood Platelets

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Tara Deans
Credit: Dan Hixson/University of Utah College of Engineering, Salt Lake City

When cancer cells spread to new parts of the body in a process called metastasis, they often get there by traveling through the bloodstream. To avoid alerting the immune system and possibly triggering their demise, cancer cells coax circulating blood platelets to glom onto their surfaces and mask them from detection. This deceptive arrangement has raised a tantalizing possibility: What if blood platelets could be programmed to recognize and take out those metastasizing cancer cells?

Tara Deans, University of Utah, Salt Lake City, was recently awarded a 2019 NIH Director’s New Innovator Award to do exactly that. It’s an exciting opportunity for a researcher who stumbled onto this innovative strategy quite by accident.

Deans is a bioengineer and expert in designing synthetic gene circuits. These circuits consist of small collections of genetic “parts” that can be assembled and integrated to program cells to behave differently than their natural counterparts [1]. In her initial work, Deans got these specialized gene circuits to prompt blood-forming stem cells to mass-produce platelets in the lab.

But blood platelets are unusual cells. They’re packed with many proteins that help to repair small nicks in blood vessels and stop the bleeding when we’re injured. Blood platelets do so even though they lack a nucleus and DNA to encode and make any of the proteins. Their protein cargo is pre-packaged and comes strictly from the bone marrow cells, called megakaryocytes, that produce them.

Deans realized that engineering platelets might pose a rare opportunity. She could wire the needed circuitry into the blood-forming stem cells and engineer them to make any desired therapeutic proteins, which are then loaded into the blood platelets for their 8- to 10-day lifespan. She started out producing blood platelets that could safely carry functional replacement enzymes in people with certain rare metabolic disorders.

As this research progressed, Deans got some troubling personal news: A friend was diagnosed with a blood cancer. At the time, Deans didn’t know much about the diagnosis. But, in reading about her friend’s cancer, she learned how metastasizing tumor cells interact with platelets.

That’s when Deans had her “aha” moment: maybe the engineered platelets could also be put to work in preventing metastasizing tumor cells from spreading.

Now, with her New Innovator Award, Deans will pursue this novel approach by engineering platelets to carry potentially promising cancer-fighting proteins. In principle, they could be tailored to fight breast, lung, and various other cancer types. Ultimately, she hopes that platelets could be engineered to target and kill circulating cancer cells before they move into other tissues.

There’s plenty of research ahead to work out the details of targeting the circulating cancer cells and then testing them in animal models before this strategy could ever be attempted in people. But Deans is excited about the path forward, and thinks that platelets hold great promise to function as unique drug delivery devices. It has not escaped her notice that this approach could work not only for controlling the spread of cancer cells, but also in treating other medical conditions.

Reference:

[1] Genetic circuits to engineer tissues with alternative functions. Healy CP, Deans TL. J Biol Eng. 2019 May 3;13:39.

Links:

Metastatic Cancer (National Cancer Institute/NIH)

Deans Lab (University of Utah, Salt Lake City)

Deans Project Information (NIH RePORTER)

NIH Director’s New Innovator Award (Common Fund)

NIH Support: Common Fund; National Cancer Institute


Are Some Tumors Just ‘Born to Be Bad’?

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Human Colon Cancer Cells

Caption: Human colon cancer cells.
Credit: National Cancer Institute, NIH

Thanks to improvements in screening technologies and public health outreach, more cancers are being detected early. While that’s life-saving news for many people, it does raise some important questions about the management of small, early-stage tumors. Do some tumors take a long time to smolder in their original location before they spread, or metastasize, while others track to new, distant, and dangerous sites early in their course? Or, as the authors of a new NIH-funded study put it, are certain tumors just “born to be bad”?

To get some answers, these researchers recently used genomic data from 19 human colorectal tumors (malignant and benign) to model tumor development over time [1]. Their computer simulations showed that malignant tumors displayed distinctive spatial patterns of genetic mutations associated with early cell mobility. Cell mobility is a prerequisite for malignancy, and it indicates an elevated risk of tumors invading the surrounding tissue and spreading to other parts of the body. What’s more, the team’s experimental work uncovered evidence of early abnormal cell movement in more than half of the invasive tumors.

Much more remains to be done to validate these findings and extend them to other types of cancer. But the study suggests that spatial mutation patterns may someday prove useful in helping decide whether to pursue aggressive treatment for early-stage cancer or opt for careful monitoring instead.


Cool Videos: Spying on Cancer Cell Invasion

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Spying on Cancer Cell Invation

If you’re a fan of the Mission: Impossible spy thrillers, you might think that secret agent Ethan Hunt has done it all. But here’s a potentially life-saving mission that his force has yet to undertake: spying on cancer cells. Never fear—some scientific sleuths already have!

So, have a look at this bio-action flick recently featured in the American Society for Cell Biology’s 2015 Celldance video series. Without giving too much of the plot away, let me just say that it involves cancer cells escaping from a breast tumor and spreading, or metastasizing, to other parts of the body. Along the way, those dastardly cancer cells take advantage of collagen fibers to make a tight-rope getaway and recruit key immune cells, called macrophages, to serve as double agents to aid and abet their diabolical spread.


Snapshots of Life: Bring on the Confetti!

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Renal Pericytes

Credit: Heinz Baumann, Sean T. Glenn, Mary Kay Ellsworth, and Kenneth W. Gross, Roswell Park Cancer Institute, Buffalo, NY

If this explosion of color reminds you of confetti, you’re not alone—scientists think it does too. In fact, they’ve even given the name “Confetti mouse” to a strain of mice genetically engineered so that their cells glow in various combinations of red, blue, yellow, or green markers, depending on what particular proteins those cells are producing. This color coding, demonstrated here in mouse kidney cells, can be especially useful in cancer research, shedding light on subtle molecular differences among tumors and providing clues to what may be driving the spread, or metastasis, of cancer cells beyond the original tumor site.

Not only is the Confetti mouse a valuable scientific tool, this image recently earned Heinz Baumann and colleagues at the Roswell Park Cancer Institute, Buffalo, NY, a place of honor in the Federation of American Societies for Experimental Biology’s 2015 Bioart competition. Working in the NIH-funded lab of Kenneth Gross, Baumann’s team created a Confetti mouse system that enables them to manipulate and explore in exquisite detail the expression of proteins in renal pericytes, a type of cell associated with the blood filtration system in the kidney.


Creative Minds: Fighting Cancer with Supercomputers

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Amanda Randles

Amanda Randles

After graduating college with degrees in physics and computer science, Amanda Randles landed her dream first job. She joined IBM in 2005 to work on its Blue Gene Project, which had just unveiled the world’s fastest supercomputer. So fast, in fact, it’s said that a scientist with a calculator would have to work nonstop for 177,000 years to perform the operations that Blue Gene could complete in one second. As a member of the applications team, Randles was charged with writing new code to make the next model run even faster.

Randles left IBM in 2009 for graduate school, with the goal to apply her supercomputing expertise to biomedical research. She spent the next several years developing the necessary algorithms to produce a high-resolution 3D model of the human cardiovascular system, complete with realistic blood flow. Now, an assistant professor at Duke University, Durham, NC, and a 2014 NIH Director’s Early Independence awardee, Randles will build on her earlier work to attempt something even more challenging: simulating the movement of cancer cells through the circulation to predict where a tumor is most likely to spread. Randles hopes all of her late nights writing code will one day lead to software that helps doctors stage cancer more precisely and gives patients accurate personalized computer simulations that put an earlier, potentially life-saving bullseye on secondary tumors.