Nav: Home

Researchers document how melanoma tumors form

April 03, 2017

There's a reason why melanoma, the most serious type of skin cancer, is so aggressive. You just need to watch the cells in action.

Researchers at the University of Iowa did just that, documenting in real time and in 3-D how melanoma cells form tumors (See videos). The cells waste no time finding their cancerous cousins, slashing their way through a lab-prepared gel to quickly join other melanoma cells and form tumors.

The findings were published online in the journal PLOS One.

Biology professor David Soll and his team used unique computer-assisted 3-D reconstruction software to chronicle how both breast tissue cancer cells and melanoma cells form tumors. The group found the two cancers act similarly in the joining stages of tumor formation. With that knowledge, they screened more than four dozen monoclonal antibodies--unique agents that can stop cells from growing or forming tumors and can be mass produced--before finding two that block tumor creation in both types of cancer.

"It upholds our hypothesis that coalescence is so similar that there's got to be the same molecules and mechanisms that do it, and we may be able to find a drug that shuts tumor formation down without being toxic to healthy cells in the body," says Soll, the paper's corresponding author.

Soll's team, in a paper published in PLOS One in March 2015, previously showed that human breast cancer cells form tumors by extending cables--bridges of sorts--between small aggregates of cancer cells. In the current study, the group reports that melanoma cells behave in a similar way, but with variations in timing and speed.

For one, melanoma cells are on the go immediately and at all times; they appear to both divide into more cells and rush to join clusters simultaneously.

One lab test showed a single cell moving a distance three times its diameter and joining with a small cancerous cluster in just four hours. In another instance, within 72 hours, 24 individual melanoma cells or small clusters of cells had mostly repositioned themselves into one large cancerous clot--an 80 percent accretion rate.

Melanoma cells are "fast as lightning," Soll says. "They don't sit still. They've got ants in their pants."

Breast cancer cells, in contrast, are more ponderous and lumbering in both their movements and in forming tumors. In the previous paper in PLOS One, Soll's group found breast cancer cells wait on average 100 hours--dividing into more cells during much of that interval--before forming "clonal islands," or small clusters that then gradually join to form large tumors.

The reason why melanoma cells seem to always be on the move could lie in their evolutionary origin, Soll says. Melanocytes, healthy skin cells that form the pigment melanin, come from neural crest cells, which are created in the spinal column. Once programmed, melanocytes migrate through the tissue to take their place in the upper layer of the skin.

"They're professional crawlers," Soll says. "They were born to move."

Because melanoma cells are derived from melanocytes, it stands to reason that melanoma cells would retain the same mobile profile. Soll's lab tests appear to show that is the case.

Still, how melanoma cells join into tumors--whether by individual cells coming together or small or large clusters of cells doing so--follows the same pattern as breast tissue cancer cells: Cables are extended to reel in other cells or clusters.

That was an interesting revelation to Soll, who then screened 51 monoclonal antibodies before finding two, anti-beta 1 integrin/(CD29) and anti-CD44, that blocked tumor creation in both cancers.

"What's so cool is the same drug that stops breast cancer cells from undergoing coalescence also stops melanoma cells from undergoing coalescence, despite these cancers' whole history being different," Soll says. "That means there's a commonality despite the different origins. And that also means there might be a magic bullet (to stop tumor formation) for all cancers."
-end-
The paper, "Melanoma Cells Undergo Aggressive Coalescence in a 3D Matrigel Model That Is Repressed By Anti-CD44," was published online on March 6.

The research was funded by the Monoclonal Antibody Research Institute and the Developmental Studies Hybridoma Bank, the latter a national resource created by the National Institutes of Health housed at the UI.

Deborah Wessels and Daniel Lusche, both in the UI's biology department, are the paper's co-first authors. Contributing authors include Edward Voss, Spencer Kuhl, Emma Buchele, Michael Klemme, Kanoe Russell, Joseph Ambrose, and Benjamin Soll, all from the UI's biology department. Aaron Bossler, from the UI's Department of Molecular Pathology; Mohammed Milhem in the UI's Department of Internal Medicine; and Charles Goldman, with Mercy Hospital System of Des Moines, Iowa, also contributed to the research.

University of Iowa

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...