The secret of lymph: How lymph nodes help cancer cells spread

August 19, 2020

August 19, 2020 (DALLAS, TEXAS) - For decades, physicians have known that many kinds of cancer cells often spread first to lymph nodes before traveling to distant organs through the bloodstream. New research from
The
Nature, found melanoma cells that pass through the lymph nodes pick up a protective coating, allowing them to survive high levels of oxidative stress in the blood and go on to form distant tumors.

Most cancer deaths happen after cancer spreads to other parts of the body through a process known as metastasis. This occurs when cancer cells from the primary tumor spread through blood vessels or migrate through lymphatic vessels before entering the blood.

"Previous research has focused on how cancer cells metastasize through the blood, but very little was known about how these cells compare to cells that metastasize through lymphatics," says

The researchers observed how human melanoma cells behaved when injected intravenously or into the lymphatic system of mice. They found that cancer cells injected into lymph nodes had a better chance of surviving and forming tumors than those injected directly into the blood.

Researchers hypothesized this difference could be explained by the high levels of oxidative stress cancer cells experience when they migrate through the blood. Exposure to oxidative stress in the blood is one reason why metastasis is a very inefficient process in which most cancer cells die before they have an opportunity to grow at a distant site.

"After further analysis, we discovered that the oxidative stress in the blood causes the cancer cells to undergo a specific form of cell death called ferroptosis," says Jessalyn Ubellacker, Ph.D., lead author of the study and a postdoctoral researcher in the Morrison lab. "In contrast, cancer cells in lymph experience lower levels of oxidative stress and are protected from ferroptosis."

To better understand why melanoma cells undergo ferroptosis in the blood but not the lymph, researchers looked for metabolic differences between cancer cells in the blood versus the lymph. They discovered cancer cells from the lymph had higher levels of a monounsaturated fatty acid known as oleic acid, which is the main component of olive oil. They also found this monounsaturated fatty acid was incorporated into the membranes of cancer cells in the lymph. This diluted polyunsaturated fatty acids in the membranes of these cells, inhibiting the chemical reactions that lead to ferroptosis and protecting the cells.

This protective coating of oleic acid from the lymph thus allowed the cancer cells to safely enter the blood, travel to other locations, and form metastatic tumors. This explains why cancer cells often form tumors first in lymph nodes before metastasizing to distant sites through the blood: They are able to load up on antioxidants in the lymph that protect the cells when they subsequently enter the blood.

"Now that we understand more about why cancer cells are most likely to metastasize initially through lymph, it raises the possibility of treating patients with drugs that target those protective mechanisms in the lymph to inhibit the early stages of metastasis," says Morrison.
-end-

The National Institutes of Health (U01 CA228608), HHMI, CPRIT (RP170114 and RP180778), and donors to the

About CRI

Children's Medical Center Research Institute at UT Southwestern (CRI) is a joint venture of UT Southwestern Medical Center and Children's Medical Center Dallas, the flagship hospital of Children's Health. CRI's mission is to perform transformative biomedical research to better understand the biological basis of disease. Located in Dallas, Texas, CRI is home to interdisciplinary groups of scientists and physicians pursuing research at the interface of regenerative medicine, cancer biology and metabolism. For more information, visit:

Related Stories:



UT Southwestern Medical Center

Related Cancer Cells Articles from Brightsurf:

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Breast cancer cells use message-carrying vesicles to send oncogenic stimuli to normal cells
According to a Wistar study, breast cancer cells starved for oxygen send out messages that induce oncogenic changes in surrounding normal epithelial cells.

Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.

Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.

Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.

First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.

Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.

Read More: Cancer Cells News and Cancer Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.