UV light aids cancer cells that creep along the outside of blood vessels

March 10, 2014 by Shaun Mason

A new study by UCLA scientists and colleagues adds further proof to earlier findings by Dr. Claire Lugassy and Dr. Raymond Barnhill of UCLA's Jonsson Comprehensive Cancer Center that deadly melanoma cells can spread through the body by creeping like tiny spiders along the outside of blood vessels without ever entering the bloodstream.

In addition, the new research, published March 6 in the journal Nature, demonstrates that this process is accelerated when the skin cancer cells are exposed to ultraviolet light. The husband-and-wife team of Barnhill and Lugassy collaborated on the study with a team from Germany's University of Bonn led by Dr. Thomas Tuting.

It is well known that melanoma cells from an initial tumor can travel through the bloodstream to other parts of the body, where they accumulate and form new tumors. Through such metastasis, a small skin cancer can become life-threatening by spreading to the brain, lungs, liver or other organs.

Fifteen years ago, Lugassy and Barnhill first discovered and described an alternative metastatic process, which they called extravascular migratory metastasis, or EVMM, by which melanoma cells could move along the outside, or abluminal, surface of blood vessels by way of angiotropism—a biological interaction between the cancer cells and the . Since then, Lugassy and Barnhill have continued to assemble a body of scientific evidence confirming the existence of this metastatic pathway of cancer cells.

With angiotropism and EVMM, the may replace tendril-like cells called pericytes, which are normally found on the outsides of blood vessels, through a process called pericytic mimicry. Imitating the pericytes, the creep along the length of until they reach an organ or other point where they accumulate to form new tumors, "potentially explaining the delay between the detection of the primary cancer and the appearance of distant metastases," said Barnhill, a professor of pathology at UCLA.

"At first our idea was controversial," said Lugassy, a UCLA associate professor of pathology. "But mounting evidence confirming angiotropism and EVMM has revolutionized the knowledge of how cancer spreads through the body to the point that other scientists have confirmed the process in other solid-tumor cell types, such as pancreatic cancer."

In the new Nature study, EVMM was observed again by Tuting, Lugassy, Barnhill and their colleagues in a genetically engineered mouse model of melanoma. The researchers also found that the immune systems of mice exposed to ultraviolet radiation responded with inflammation that accelerated the angiotropism, increasing the level of EVMM and leading to more lung metastases than among the mice not exposed to UV light.

This study was conducted at the Laboratory for Experimental Dermatology in Bonn, under the direction of Tuting.

"We have known for a long time that UV radiation is a factor in the development of melanoma," Barnhill said, "but in this study, the melanoma was already present in the mice."

Tuting observed that UV light provoked inflammation at the site of the tumor, which caused the mouse immune system to attract a type of common known as neutrophils. The neutrophils, in turn, promoted angiotropism.

With this new knowledge—and the confirmation of Lugassy and Barnhill's research on angiotropism and EVMM—researchers in the scientific community can now begin looking for a drug target that will interfere with this EVMM process. Because the danger of melanoma comes from its metastasis from the skin to the vital organs, being able to slow down or stop this process could turn a disease that is often a death sentence into a manageable chronic illness with relatively little risk of death.

Explore further: Sunburns strike twice: Skin inflammation following UV irradiation promotes cancer cell spread along blood vessels

More information: www.nature.com/nature/journal/ … ull/nature13111.html

Related Stories

Sunburns strike twice: Skin inflammation following UV irradiation promotes cancer cell spread along blood vessels

February 26, 2014
Melanoma is particularly dangerous because it can form metastases in vital organs such as the lungs, liver or brain. UV radiation is considered to be the most significant triggering factor. An interdisciplinary team of researchers ...

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 ...

Long-term study confirms success of method for detecting spread of deadly skin cancer

March 4, 2014
Research at UCLA on a technique for detecting the earliest spread of melanoma, the deadliest form of skin cancer, has confirmed that the procedure significantly prolongs patients' survival rates compared with traditional ...

Tumors form advance teams to ready lungs for spread of cancer

August 15, 2013
Cancer metastasis requires tumor cells to acquire properties that allow them to escape from the primary tumor site, travel to a distant place in the body, and form secondary tumors. But first, an advance team of molecules ...

The number of tumor cells spread to sentinel lymph nodes affects melanoma prognosis

February 18, 2014
Cancer cell spread to the sentinel node—the lymph node to which cancer cells are most likely to spread from a primary tumor—is a risk factor for melanoma death. According to a study published in this week's PLOS Medicine ...

Recommended for you

Clear link between heavy vitamin B intake and lung cancer

August 22, 2017
New research suggests long-term, high-dose supplementation with vitamins B6 and B12—long touted by the vitamin industry for increasing energy and improving metabolism—is associated with a two- to four-fold increased lung ...

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

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.