Observing the mechanism of metastasis for the first time

August 7, 2018, American Institute of Physics
In this image, hierarchical clustering analysis of gene expression in tumor cells (left), hybrid cells (center) and normal mouse tissue cells (right), when compared to the average expression of all genes in the display. Credit: Gabriel Jacobs, Tanner McArdle and Brian T. Freeman

Metastasis, or the formation of secondary tumors, is a leading contributor to the vast majority of deaths related to cancer. The exact mechanisms for how broken cellular function appears in cells far removed from a cancer's primary tumor remain an area of ongoing research. New work looks to explain a century-old hypothesis for how cancer forms hybrids within the body, leading to metastasis.

Researchers from the University of Minnesota Twin Cities confirmed a link between healthy-tumor hybrid cells and metastatic tumors for the first time in live animals. In APL Bioengineering, the team discusses how they studied the distinct, heterogenous gene expression profiles found in human hybrid cells and how hybrid cells spontaneously occur in mouse models.

"The research community is recognizing that heterogeneity can make tumors very hard to treat," said Brenda Ogle, one of the authors on the paper. "Instead of creating many different therapies to target different tumor cell types, it might be possible to quell heterogeneity at the source by limiting hybrid formation in the tumor."

Nearly 100 years ago, one theory suggested that some spontaneously caused secondary tumors by fusing their cellular material with regular cells and re-establishing their errant gene expression. It was only in recent years that sequencing technology and reporter molecules were advanced enough to tackle the topic.

To address these questions, Ogle and her colleagues first cultured and tumor cells that spontaneously fused to form hybrids. Using a technique called RNA-seq, the group took a molecular snapshot of the of each fused hybrid cell.

The resulting hybrids were found to express the genes of both the healthy cell and the tumor cell. This factor aids metastatic cells in surviving the primary and potentially helping lay the groundwork for other .

The group then engineered mice that produced an inducible reporter enzyme called luciferase when hybrids were present. This allowed the team to track hybrid formation in living animals for the first time. Rather than using bioluminescent macroscopic imaging, which lacks the sensitivity to detect cells scattered across a specimen, they developed a technique that stitched together hundreds of microscopic images to detect luciferase.

Sites where the mice expressed luciferase lit up, indicating that hybrid cells were forming spontaneously in vivo. The metastases showed a significantly higher proportion of hybrid cells than the .

"When hybrids form, cytoplasmic and nuclear material of two cells are forced to reorganize into one cell," Ogle said. "Some of those cells can suddenly go gangbusters and start proliferating and moving more actively than their parent ."

Ogle said the group hopes their findings will lead to further research on how hybrids form, since the development of drugs to inhibit hybrid formation might prevent metastatic spread.

Explore further: Researchers report on tumor transition states

More information: "Breast tumor cell hybrids form spontaneously in vivo and contribute to breast tumor metastases," APL Bioengineering, DOI: 10.1063/1.5024744

Related Stories

Researchers report on tumor transition states

April 19, 2018
Tumor heterogeneity describes the differences between different cells within a given tumor. These differences have major implications for the diagnosis, prognosis, and therapy of cancer patients. Different mechanisms have ...

Engineered cancer cells can fight primary and metastatic cancer

July 11, 2018
What if cancer cells could be re-engineered to turn against their own kind? A new study led by researchers at Brigham and Women's Hospital leverages the power of gene editing to take a critical step toward using cancer cells ...

How cancer spreads: Metastatic tumor a hybrid of cancer cell and white blood cell

June 27, 2013
Yale Cancer Center scientists, together with colleagues at the Denver Police Crime Lab and the University of Colorado, have found evidence that a human metastatic tumor can arise when a leukocyte (white blood cell) and a ...

Clue to how cancer cells spread

January 27, 2017
In a second human case, a Yale-led research team has found that a melanoma cell and a white blood cell can fuse to form a hybrid with the ability to metastasize. The finding provides further insight into how melanoma and ...

Metastatic lymph nodes can be the source of distant metastases in mouse models of cancer

March 22, 2018
A study by Massachusetts General Hospital (MGH) investigators finds that, in mouse models, cancer cells from metastatic lymph nodes can escape into the circulation by invading nodal blood vessels, leading to the development ...

Cancer metastasis: Cell polarity matters

February 28, 2018
It's not only the number of migrating cancer cells that determines the risk for metastasis, but also their characteristics, scientists from the German Cancer Research Center (DKFZ) report in Nature Communications. For circulating ...

Recommended for you

First immunotherapy success for triple-negative breast cancer

October 21, 2018
There is new hope for people with an aggressive type of breast cancer, as an immunotherapy trial shows for the first time that lives can be extended in people with triple-negative breast cancer.

Healthy diets linked to better outcomes in colorectal cancer

October 20, 2018
Colorectal cancer patients who followed healthy diets had a lower risk of death from colorectal cancer and all causes, even those who improved their diets after being diagnosed, according to a new American Cancer Society ...

Why some cancers affect only young women

October 19, 2018
Among several forms of pancreatic cancer, one of them specifically affects women, often young. How is this possible, even though the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, known ...

Scientists to improve cancer treatment effectiveness

October 19, 2018
Together with researchers from the University of Nantes and the University of Reims Champagne-Ardenne in France, experts from the National Research Nuclear University MEPhI have recently developed a quantum dot-based microarray ...

Mutant cells colonize our tissues over our lifetime

October 18, 2018
By the time we reach middle age, more than half of the oesophagus in healthy people has been taken over by cells carrying mutations in cancer genes, scientists have uncovered. By studying normal oesophagus tissue, scientists ...

Study involving hundreds of patient samples may reveal new treatment options of leukemia

October 17, 2018
After more than five years and 672 patient samples, an OHSU research team has published the largest cancer dataset of its kind for a form of leukemia. The study, "Functional Genomic Landscape of Acute Myeloid Leukemia", published ...

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.