Watch cancer spread in a mouse

July 5, 2017

Researchers in Japan have developed a method to image cancer at the single-cell level by using chemical techniques to make whole mouse bodies and organs highly transparent. Combining their preparation with existing imaging technology, they were able view cancer cells multiplying within organs, including the lungs, intestines, and liver, and traveling through the body to and from new tumors in distant locales. The work appears July 5 in Cell Reports.

"The study demonstrates the power of whole-body and whole-organ clearing and imaging with single-cell resolution," says co-corresponding author Hiroki Ueda (@hiroking1975), of the University of Tokyo and the RIKEN Quantitative Biology Center. The research team achieved single-cell resolution for models that grow and metastasize in different ways. The images reveal cancerous colonies in enough detail to calculate their shapes, volumes, and distributions—characteristics critical to distinguishing between patterns of metastasis.

For example, the researchers used the platform to generate a whole-mouse scan of spreading into the liver and throughout the abdomen. Another set of images shows a healthy pair of lungs being gradually colonized by cancer cells over the course of two weeks, while a third probes relationships between cancer cells and blood vessels inside the brain.

Picturing individual cancer cells during metastasis is challenging because they can be scattered all over an entire body. Locating the cancer cells relies on picking up signals from fluorescent proteins that they express, signals that must be preserved when applying tissue clearing methods in pursuit of higher resolution.

Whole-body imaging of the spontaneous metastasis model with orthotopic injection of Renca cells in BALB/c mice. Whole-body imaging is shown (Renca: mCherry, nuclei: RedDot2). Credit: Hiroki R. Ueda et al.

Given this difficulty, the research team, which included co-first authors postdoc Shimpei Kubota and project researcher Kei Takahashi, took a chemical mixture called CUBIC (Clear Unobstructed Brain/Body Imaging Cocktail) that they had previously developed for whole-body imaging preparation and optimized its composition for detecting and viewing cancer cells. Upon using the modified mixture to turn tissues and vital organs clear, the researchers were able to pluck out fluorescence signals and locate cancer cells in places such as the liver, pancreas, and intestines.

The new imaging protocol is already providing a clearer view of certain mysterious steps of metastasis. In particular, in order to reach a new site within the body and metastasize, a cancer cell must surf the bloodstream, entering and exiting through blood vessel walls.

"Most are not so lucky and die during the trip," says co-corresponding author Kohei Miyazono, of the University of Tokyo, "But obtained through the new method suggest that treated with TGF-beta, a protein that regulates cellular growth and differentiation in humans and is produced in increased quantities by some cancers, are far more likely to survive the journey and form malignant outposts."

Whole-brain imaging of the experimental brain metastasis models with MDA-231-D cells in BALB/c-nu/nu mice. The 3D images of the brain samples are shown (cancer cell: mCherry, α-SMA: FITC, nuclei: RedDot2). Credit: Hiroki R. Ueda et al.

With preliminary investigations already underway, the researchers say that cancer imaging and analysis using the CUBIC protocol will lead to further insight into the complexities and nuances of metastatic pathways. The technique might also shed light on single-cell processes related to other diseases or medical fields. "We believe that same strategy will be applicable to other biomedical studies such as autoimmunity and regenerative medicine, in which the single-cell events play crucial roles," says Ueda.

Explore further: Study sheds light on how ovarian cancer spreads

More information: Cell Reports, Kubota et al.: "Whole-body profiling of cancer metastasis with single-cell resolution" http://www.cell.com/cell-reports/fulltext/S2211-1247(17)30806-9 , DOI: 10.1016/j.celrep.2017.06.010

Related Stories

Study sheds light on how ovarian cancer spreads

June 27, 2017
With 20,000 diagnoses each year, ovarian cancer is the ninth most common cancer and fifth leading cause of cancer death among women in the United States. So many women die from ovarian cancer because it often goes undetected ...

Immune cells localized near pancreatic cancer cells have altered metabolism, could promote cancer

May 9, 2017
A diagnosis of pancreatic cancer is a virtual death sentence, with only 3 to 5 per cent of patients surviving beyond five years. A key reason that it has the lowest survival rate of all major cancers is that it readily spreads ...

Japan scientists make see-through mice

November 6, 2014
Researchers at the RIKEN Quantitative Biology Center in Japan, together with collaborators from the University of Tokyo, have developed a method that combines tissue decolorization and light-sheet fluorescent microscopy to ...

Study reveals mechanisms cancer cells use to establish metastatic brain tumors

February 27, 2014
New research from Memorial Sloan Kettering provides fresh insight into the biologic mechanisms that individual cancer cells use to metastasize to the brain. Published in the February 27 issue of Cell, the study found that ...

Before a cure, a crusade to stop lung cancer from spreading

November 11, 2016
The American Cancer Society has reported that lung cancer, which kills more Americans than any other type of cancer, is expected result in an estimated 158,080 deaths in 2016.

Recommended for you

One in five young colon cancer patients have genetic link

December 13, 2017
As doctors grapple with increasing rates of colorectal cancers in young people, new research from the University of Michigan may offer some insight into how the disease developed and how to prevent further cancers. Researchers ...

New strategy for unleashing cancer-fighting power of p53 gene

December 13, 2017
Tumor protein p53 is one of the most critical determinants of the fate of cancer cells, as it can determine whether a cell lives or dies in response to stress. In a new study published today in the journal Nature Communications, ...

Researchers develop test that can diagnose two cancer types

December 12, 2017
A blood test using infrared spectroscopy can be used to diagnose two types of cancer, lymphoma and melanoma, according to a study led by Georgia State University.

Cancer-causing mutation suppresses immune system around tumours

December 12, 2017
Mutations in 'Ras' genes, which drive 25% of human cancers by causing tumour cells to grow, multiply and spread, can also protect cancer cells from the immune system, finds a new study from the Francis Crick Institute and ...

Atoh1, a potential Achilles' heel of Sonic Hedgehog medulloblastoma

December 12, 2017
Medulloblastoma is the most common type of solid brain tumor in children. Current treatments offer limited success and may leave patients with severe neurological side effects, including psychiatric disorders, growth retardation ...

MRI scans predict patients' ability to fight the spread of cancer

December 12, 2017
A simple, non-invasive procedure that can indicate how long patients with cancer that has spread to the brain might survive and whether they are likely to respond to immunotherapy has been developed by researchers in Liverpool.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.