cancer stem cells

For brain tumors, origins matter

by Heather Buschman, Ph.D. on November 12, 2012 at 6:19 am | 2 Comments

Left: Medulloblastoma tumor (green) from untreated mouse. Right: Corresponding tissue from mouse treated with bFGF lacks tumor growth.

Brain tumors arising from different cell types might require different—and more personalized—treatment approaches.

Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival. But the particular cell this mutation happens in—the cell of origin—can have an enormous impact on the behavior of the tumor, and on the strategies used to treat it.

Robert Wechsler-Reya, Ph.D., professor and director of the Tumor Development Program in Sanford-Burnham’s NCI-designated Cancer Center, and his team study medulloblastoma, the most common malignant brain cancer in children. A few years ago, they made an important discovery: medulloblastoma can originate from one of two cell types: 1) stem cells, which can make all the different cell types in the brain or 2) neuronal progenitor cells, which can only make neurons.

Stem cells and progenitor cells are regulated by different growth factors. So, Wechsler-Reya thought, maybe the tumors arising from these cells respond differently to different therapies…

The zombies of cancer research

by Heather Buschman, Ph.D. on October 31, 2012 at 3:15 pm | 4 Comments

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Conventional therapies don't hit tumors in the right place - at the cancer stem cells - so they keep coming back

The scientific symposium portion of San Diego’s annual Stem Cell Meeting on the Mesa fell on Halloween this year—good timing for a discussion about the dark side of stem cells: cancer stem cells.

Robert Wechsler-Reya, Ph.D., director of Sanford-Burnham’s Tumor Development Program, once said, “Current cancer therapies are like trying to kill a zombie by kicking it in the shins.”

Everyone knows you can only kill a zombie with a shot to the brains—anywhere else might slow it down temporarily, but only a very targeted hit to the head will get rid of it for good. (See the CDC’s Zombie Preparedness Guide.) So what Wechsler-Reya means is that the current methods for destroying or removing tumor cells are not aimed at what may, in some cases, be the actual “brains” of the problem—cancer stem cells.

Like other types of stem cells, cancer stem cells can self-renew, producing more cells. They also differentiate, specializing into other cell types. Those are very useful features when scientists are using stem cells to repair or replace diseased or damaged tissue (rebuilding heart muscle tissue after a heart attack, for example). However, cellular proliferation is also a hallmark of cancer.

In some cancers, stem cells may be the initial source of the problem, giving rise to tumors. They might also be the reason some tumors are resistant to standard cancer therapies such as chemotherapy or radiation therapy. What’s more, cancer stem cells can allow tumors to recur—even if the bulk of a tumor is removed, a few remaining cancer stem cells rise up to rebuild a new tumor. Like zombies, they are hard to get rid of.

Scientists are now trying to learn how stem cells turn to the dark side in cancer so that they can figure out how to better detect, prevent, and treat tumor growth—targeting the zombie’s brains, not just its shins.

Meet the four cancer stem cell (zombie)-fighting scientists who spoke at the 2012 Stem Cell Meeting on the Mesa:

Tales from the intestinal crypt

by Heather Buschman, Ph.D. on April 14, 2011 at 7:46 am | 0 Comments

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Cells proliferating in an intestinal crypt (blue) (Image courtesy of the Oshima lab)

Doctors have noticed for decades that people with Down Syndrome seldom develop cancers. Down Syndrome results from an extra copy of chromosome 21, leading scientists to wonder if something about that particular piece of the genome could protect against cancer. A few years ago, researchers at Johns Hopkins University tested that hypothesis. They added several different chromosome fragments from the mouse equivalent of human chromosome 21 to mice that are susceptible to colon tumors until they narrowed down its protective effect to just 33 genes– including one called Ets2.

Meanwhile, Dr. Robert Oshima and his team were already studying Ets2 and its role in breast cancer, where Ets2 does the opposite – it promotes tumor formation. Intrigued by the new and seemingly paradoxical findings in colon cancer, they started looking at mice bred to lack Ets2 only in intestinal cells.

“Our initial results were the complete opposite of what we expected,” says Dr. Jorge Múnera, former graduate student in the Oshima lab and now postdoctoral researcher in Dr. Hudson Freeze’s group. “Unlike what we saw in our breast cancer model, Ets2-deficient mice clearly had more colon tumors.”

Got MELK?

by Heather Buschman, Ph.D. on January 19, 2011 at 2:51 pm | 3 Comments

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Not all cells in a tumor are equal. They have different genes, proteins and behaviors and while some are easily killed, others are more resistant to cell-destroying therapies. In some cancers, a few of these hardier cells are cancer stem cells and they may be the culprits behind tumor formation and drug resistance. Much like other types of stem cells, cancer stem cells can do two things: self-renew (generating more new stem cells) and differentiate (giving rise to a variety of cell types). The trick to better understanding tumor formation, and designing drugs that specifically target cancer at its root, is figuring out how to pick the stem cell needle out of the tumor haystack. Sanford-Burnham researchers Dr. Alexey Terskikh and Dr. Robert Oshima think a protein called MELK, short for maternal embryonic leucine zipper kinase, might allow them to do just that.

Dr. Terskikh has studied MELK for almost 10 years, but it hasn’t been easy. Early on, researchers would disrupt MELK in mice but see no consequences from that disruption. Now, in a recent paper published in the journal Cancer Research, Dr. Terskikh, Dr. Oshima, and their colleagues show that MELK protein levels are particularly high in tumor-initiating cells found in a mouse model of breast cancer.

“Previous studies provided evidence that high MELK levels correlate with poor prognosis in breast and brain tumors,” Dr. Terskikh says. “Now we show for the first time that MELK does actually play a role in mammary tumor initiation and progression in a relevant animal model of breast cancer.”

Differentiation therapy: a different approach to treating tumors

by Heather Buschman, Ph.D. on September 6, 2010 at 3:00 pm | 9 Comments

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What if the best way to stop a tumor is not to kill it, but to turn it into something else? That’s the idea behind differentiation therapy, a novel concept that targets cancer stem cells. Scientists at Sanford-Burnham and elsewhere are beginning to think that stem cells may be the culprit behind tumor formation in some cancers. Much like other types of stem cells, cancer stem cells are presumably able to do two things: 1) self-renew, generating more new stem cells and 2) differentiate, giving rise to a variety of cell types. Differentiation therapy attempts to end the cycle of self-renewal by encouraging the cells to settle down and become a specific cell type, such as a skin cell.

“It seems to me that if we are smart enough to know all the genes in a cell, we should be smart enough to tell the cell what to do,” says Dr. Robert Oshima, co-director of the Sanford-Burnham Cancer Center’s Tumor Development Program. “In differentiation therapy, we are essentially telling cells: ‘Don’t become criminals, become productive members of society. If you stay legal, we’ll leave you alone.’”

Tumors Beware, Part 2

by Heather Buschman, Ph.D. on August 23, 2010 at 1:28 pm | 0 Comments

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Last week we mentioned a lecture Dr. Kristiina Vuori, Sanford-Burnham’s president and director of our NCI-Designated Cancer Center, gave to San Diego’s CONNECTcommunity about the Institute’s many exciting advances in cancer research.So how exactly do Sanford-Burnham researchers put cancer cells in their place?

As Dr. Vuori highlighted in her lecture, scientists in each of Sanford-Burnham Cancer Center’s four programs – Tumor Development, Signal Transduction, Tumor Microenvironment and Apoptosis and Cell Death Research – are designing new therapies that tackle cancer during every step of the disease’s progression. Here are just a few examples of Sanford-Burnham’s multi-pronged approach, as described by Dr. Vuori…

For brain tumors, origins matter

The zombies of cancer research

Tales from the intestinal crypt

Got MELK?

Differentiation therapy: a different approach to treating tumors

Tumors Beware, Part 2

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For brain tumors, origins matter

The zombies of cancer research

Tales from the intestinal crypt

Got MELK?

Differentiation therapy: a different approach to treating tumors

Tumors Beware, Part 2

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