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Tracing Cancer Back to Its Origins
Mon, 01/12/2015 – 9:23am
Columbia UniversityUsing different colored “dyes,” researchers are tracing cancers back to their original cells. Source: Cathy Mendelsohn/Columbia University
Using different colored “dyes,” researchers are tracing cancers back to their original cells. Source: Cathy Mendelsohn/Columbia UniversitySome bladder cancers look like tiny fingers. Others look like flat bed sheets.
The differences are obvious and they have clinical implications. The “fingers” of papillary tumors often grow back after surgery, but flat carcinoma in situ cancers are typically more aggressive and more likely to spread.
“The big question is why,” said Cathy Mendelsohn, PhD, a professor of urology, pathology & cell biology, and genetics & development, who has been studying bladder development and regeneration at Columbia. “Because if we understand how cancers arise, and why some lesions invade and others don’t, we may be able to develop more precise techniques for diagnosis and better therapies for treatment.”
Most research into tumor diversity delves into the mutations the cancer acquires as it evolves from a single cell to a complex tissue. And indeed, cancers often behave differently depending on the types of mutations they’ve acquired.
But in the last decade, growing evidence suggests that the type of cell in which the cancer originates also shapes the cancer’s traits and susceptibility to treatment.
“If this is true, you can see why identifying the cell of origin might have clinical relevance,” said Michael Shen, PhD, professor of medicine, genetics & development, and urology, who has been searching for the starter cells of prostate cancer.
But identifying each cancer’s “cell of origin” has been tricky. For one thing, said Shen, “looks can be deceiving.” For example, for years it was assumed that “basal-type” breast cancers spring from the breast’s basal cells because most of the cancer’s cells resembled—on a molecular level—normal basal cells. Yet recent work shows that basal-like breast cancers actually originate in a completely different source, luminal cells.
Instead of relying on what cells look like, Mendelsohn and Shen are exploiting newer technology— fate-mapping—that allows them to label specific types of cells with an indelible marker that is passed on to each one of the cells’ progeny.
By marking cells early in mouse development and then waiting for cancer to develop, the researchers simply looked inside the cancer to find the label and identify the original cell type.
In the bladder, this method revealed not one (as originally thought), but two types of cells that give rise to cancer. The bottom-most cells of the bladder’s inner lining—K5 basal cells—give rise to flat carcinoma in situ tumor, considered to be precursors of invasive bladder cancers, while cells in the middle of the lining—called intermediate cells—give rise to the protruding papillary cancers that are considered less invasive than carcinoma in situ.
“These findings help explain why these lesions look and behave differently,” said Mendelsohn “Because we are using mouse models, it will now be possible to pull labeled cells out of these lesions before they become invasive, to see which mutations drive aggressive behavior.”
Researchers can now also use the cells to make organoids, tiny 3-dimensional cultures of cells that mimic the properties of tumors. “With organoids that behave like tumors, we may be able to speed up drug screening tremendously,” said Shen.
After using fate-mapping to identify the cells that give rise to most prostate cancers, Shen has recently created organoids that respond to chemotherapy in the same way as prostate cancers do in some human patients.
“By reducing prostate cancer to a dish, we can now do experiments that take only weeks, not years, to finish.”
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6 Replies
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You are so very welcome! If we didn’t have a sense of humor, we would all go bananas. I already feel like a lab monkey!! GIVE ME A BANANA!!!!!!!
T1,NO,MO battling bladder cancer since 2005
Thank you diseldoc for always bringing a smile to my face in this dismal world of BC.
I guess the should call it slower invasive.? Maybe!
T1,NO,MO battling bladder cancer since 2005
Yes, that is how I understand it as well. Unlike CIS which is always high grade, and much greater chance to become invasive.
Anne
I believe papillary just refers to the visible appearance of the tumour, usually wart or mushroom like and growing into the interior of the bladder, but at the same time the tumour can be growing into the layers of the bladder.If they are not diagnosed and treated they have the capacity to grow through theses layers and spread to other parts of the body.The majority of papillary tumours are low grade upon diagnosis, meaning that they grow relatively slowly , so monitoring to check for reappearance following surgery is important so they can be nipped in the bud, before they have chance to grow deep, or progress to a more aggressive form.I would say that a better way to describe them would be “potentially” less invasive.
Interesting research. But I thought that papillary tumors are not invasive. Here in the article it says less invasive.
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