Imaging: Cancer caught in the act

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Methods for monitoring tumour cells in living animals are transforming our view of cancer.

Mikala Egeblad was blown away when she made her first action film of tumour cells inside live mice. Until then, she had studied samples on microscope slides, where the cells sat still, frozen in time. But seeing them in a living animal brought the cells to life. “You turn on the microscope and look in the live mouse and suddenly these same cells are running around like crazy,” says Egeblad, a cancer researcher at Cold Spring Harbor Laboratory in New York. “It really changed my thinking.”

Increasingly, cancer researchers are embracing the chance to spy on individual tumour cells in their native environment. In studies of static tissue cultures, investigators have to infer what cancer and other cells surrounding the tumour might be doing, and how they might be interacting. Tracking cancer in live animals over time — an approach called intravital imaging — puts those interactions on display, and allows biologists to zoom in on the small number of dangerous cells within a tumour that drive the disease or resist treatment.

The technique is young, and labs are still working out how best to analyse the gigabytes of video data it generates. But the increasing use of intravital imaging over the past decade has already helped researchers to piece together timelines for key cellular and molecular events, such as the process by which tumour cells sneak into blood vessels. Such clues have yielded new hypotheses about how cancers grow, spread and resist treatment — information that could, for example, eventually enable drug developers to understand why some cancer cells do not succumb to therapy.

And in a video-obsessed culture, the imaging technique holds instant appeal. “When we show our movies, people fall out of their seats when they see how dynamic a tumour lesion can be,” says Peter Friedl at Radboud University Nijmegen in the Netherlands. “It's a change in perception.”

Deep dive

First used by cancer biologists in the late 1990s, intravital imaging involves focusing powerful microscopes directly onto exposed tissue in a live, anaesthetized mouse. More labs have adopted intravital imaging as technological improvements have made it possible to peer further into tissue — now as many as 20 cells deep — and to tease out fainter signals. A growing library of molecular markers has given researchers the ability to visualize up to eight different kinds of cells and structures, including various immune-system cells and the endothelial cells that line blood vessels. “The markers and the microscopy technology make this a powerful combination,” says Frederic de Sauvage, vice-president of molecular oncology at the biotechnology company Genentech in South San Francisco, California, who has seen the technology in action.

Putting these components together creates a comprehensive picture of cancer as a complex ecosystem of cells that migrate, proliferate and interact. Although cancer researchers have long understood that cells in a tumour are genetically heterogeneous, intravital imaging is revealing how the behaviour of individual cells can also differ. For example, cancer cells may march in single file or collectively as a tight-knit group, depending on the type of tumour and its environment.

One mysterious cellular behaviour that has landed in the sights of these microscopes is that of the macrophage, a type of immune cell that normally engulfs pathogens, removes dead cells and stimulates immune responses. Macrophages can incite immune cells to fight cancer, but more often they boost a tumour's growth and spread.

Intravital imaging studies showed that macrophages, along with tumour cells and endothelial cells, form a structure that pumps tumour cells into the bloodstream — a key step in metastasis. Working with rodents, researchers led by John Condeelis at Albert Einstein College of Medicine in New York found that when macrophages come into contact with mammary tumour cells, the tumour cells become more invasive, degrading the protein-rich matrix around blood vessels and squeezing between the endothelial cells. Macrophages cause the endothelial cells to lose contact with each other, opening a hole in the vessel wall and allowing tumour cells to stream out of the tissue and into the bloodstream12.

Condeelis's team has shown that this 'pump' is present in human breast cancer. The group has also identified three molecular markers, one for each cell type in the structure, that indicate its presence in tumours. In a study3 of 60 people with breast cancer, individuals with a higher density of these pumps in their tumours were more likely to develop metastases in other organs. A start-up company, MetaStat in Montclair, New Jersey, has licensed this prognostic technology and is developing a test that predicts metastatic risk in people with breast cancer. The company hopes to have the test in clinical trials by the end of this year. Condeelis's group is also working on a probe to identify the pumps using magnetic resonance imaging, avoiding the need to take tissue biopsies from patients.

Written By: Corie Lok
continue to source article at nature.com

15 COMMENTS

  1. Having made it through a form of cancer myself and currently being surrounded by colleagues going through it, I am always in awe of the amazing people working in this field. Their hard work will mean fewer people suffering unpleasant treatments and unpleasant deaths. Count me as ‘blown away’ too. How wonderful!

  2. Next month my daughter starts work as Research Assistant in the Biophysics department of the Science Faculty at Oxford university England.

    Who knows, she might have arrived on the scene, albeit in a junior capacity, at a crucial moment in cancer research.

    But even if not, after working so incredibly hard all her academic career, she’s finally doing exactly the kind of work she’s passionate about.

    She is very happy indeed; as am I for her!

  3. It’s terrifying to see how cancer cells behave; they really mean business!

    I had a friend who was killed by prostate cancer, and at a certain stage that particular form suddenly metastasizes into the bones causing an agonizing death.

    His father died of it, so he had had tests carried out every six months, but tragically, to no avail.

    Both father and son had been funeral directors, so knew from Post-Mortem results over many years the prevalence and effects of the various forms of the disease.

    I consulted my GP about having mine removed – it’s served its purpose in my case – but for obvious reasons, no surgeon will remove a healthy organ.

    So chaps, we’re stuck with this dis-functional product of evolution up our bums.

    If creationists want evidence of evolution by means of natural selection, or, just how stupid their god would have to be to have “designed” such a plumber’s nightmare, there’s no better place for them to look to find it; and while they’re about it they can kiss my arse!

    • In reply to #4 by Stafford Gordon:

      If creationists want evidence of evolution by means of natural selection, or, just how stupid their god would have to be to have “designed” such a plumber’s nightmare, there’s no better place for them to look to find it; and while they’re about it they can kiss my arse!

      A plumber’s nightmare is right. As Neil DeGrasse Tyson once put it: it’s like placing an entertainment center in the middle of a sewer (I’m paraphrasing here). What engineer in his right mind would design a system that uses the same pipes for the elimination of the body’s waste products and passage of the seed of life. Biologically, that’s like putting all your eggs in the same basket.

      Having a problem with one of the functions of the uro-genital system will automatically impact on the other one. A urinary tract or bladder infection will impact on the reproductive functions. Having a problem with a reproductive component of the system, the prostate, will negatively affect elimination.

      In this respect, a woman’s anatomy is better “designed” than that of a man since elimination and reproduction use 2 independent set of “pipes”.

      Oh BTW, happy to hear about your daughter’s achievement. That is no small feat, the kind that would make any father exceedingly proud.

      • In reply to #10 by NearlyNakedApe:

        In this respect, a woman’s anatomy is better “designed” than that of a man since elimination and reproduction use 2 independent set of “pipes”.

        Independent maybe, but in close proximity. :-)

  4. My husband has recently been diagnosed with lung cancer, so this setting has suddenly become our world; a world of tests and treatment. I’m blown away by the advances that are happening every day. We are very fortunate that it has been caught early and it has not metastasised. His chances are better than even, so we are very hopeful.

    • In reply to #5 by Nitya:

      It should be known, I hold you in the highest regard, due to your countless brilliant contributions to conversation here. Thoughts are with you and your husband. I wish you both, the best possible outcome regarding this matter. May you have long, happy lives and receive the knowledge, fun, rewards, and acknowledgement you both deserve. Best wishes, Nitya.

      Tim

      • _In reply to #7 by Timothy McNamara:_and #6 LaurieB

        In reply to #5 by Nitya:

        Thank you very much for your kind thoughts Tim and Laurie. You may have noticed that the frequency of my comments has escalated of late? The act of having to put my thoughts into words is a great distraction and I’ve found that completely focussing on a reply takes all my concentration. Perhaps this knowledge could back-up a study somewhere.

        • In reply to #8 by Nitya:

          In reply to #7 by Timothy McNamara:and #6 LaurieB

          In reply to #5 by Nitya:

          Thank you very much for your kind thoughts Tim and Laurie. You may have noticed that the frequency of my comments has escalated of late?

          We benefit the most whenever you contribute I reckon. Splendid effort by you and David opposing bigotry on another thread. Bravo.

          I share the sentiments others have expressed and I sincerely appreciate your mind and how you use it. The whole forum benefits, so thanks a lot and good luck to you both Nitya.

          • In reply to #13 by Len Walsh:

            Thank you Len and everyone who has offered us wishes of good luck. I really appreciate the positive thoughts. I’ll let you know how it goes after a few months.

            The technologies used are amazing! The method of collecting and then identifying cells is the stuff of science fiction. From that point an individual plan of treatment is designed ( for this particular case and for the type of cells present). I’m taking the advice of LaurieB and letting the force of science be with us right now. Hooray for all those medical scientists out there! People are getting many more years of life due to your hard work, so bravo!

            Regarding our long battle on that other thread; I really questioned the wisdom of continuing as I thought we were just giving oxygen to our opponent by keeping it going, but I think my body was taken over by some crusading force and I couldn’t let each further comment go unchallenged. (I’m not sure if that was the same thinking for my partner in crime David R, but I would suspect so.)

    • In reply to #5 by Nitya:

      My husband has recently been diagnosed with lung cancer, so this setting has suddenly become our world; a world of tests and treatment. I’m blown away by the advances that are happening every day. We are very fortunate that it has been caught early and it has not metastasised. His chances are bett…

      Your words really take me back to how our world contracted around us and for a year or so hospital smells and great doctors and nurses became our world, it seemed to me I had the easy role being the ill one. I’m so glad to hear it was caught early. Best of wishes to you both for a positive outcome.

    • Strength to you and your husband .Thank goodness you caught it early.My best wishes to you in a difficult time, my dear.In reply to #5 by Nitya:

      My husband has recently been diagnosed with lung cancer, so this setting has suddenly become our world; a world of tests and treatment. I’m blown away by the advances that are happening every day. We are very fortunate that it has been caught early and it has not metastasised. His chances are bett…

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