Breaking News
February 23, 2019 - Intensive therapy during early stages of MS leads to better long-term outcomes
February 23, 2019 - Prenatal Fluconazole Exposure Increases Neonatal Risks
February 23, 2019 - Mental Health Screening: MedlinePlus Lab Test Information
February 23, 2019 - Study suggests birth mechanics are part of the process that leads to autism
February 23, 2019 - Unhealthy diet linked to poor mental health
February 23, 2019 - Study gives a snapshot of crocodile evolution
February 23, 2019 - Research finds steep rise in self-poisonings among young people
February 23, 2019 - American Gastroenterological Association announces “AGA Future Leaders Program”
February 23, 2019 - Scientists uncover new mechanisms regulating neural stem cells
February 23, 2019 - Combinations of certain insecticides turn out to be lethal for honeybees
February 23, 2019 - AHA News: Why Are Black Women at Higher Risk of Dying From Pregnancy Complications?
February 23, 2019 - NIMH » Anxiety Disorders
February 23, 2019 - Autistic people urgently need access to tailored mental health support
February 23, 2019 - Newly designed molecule could benefit people with Friedrich’s Ataxia
February 23, 2019 - Chinese CRISPR twins may have better cognition and memory
February 23, 2019 - Study finds new genetic clues associated with asthma in African ancestry populations
February 23, 2019 - Fetal signaling pathways may offer future opportunities to treat lung damage
February 23, 2019 - Early-stage osteoarthritis drug wins prestigious innovation award
February 23, 2019 - Researchers report positive findings with dasotraline for ADHD in children ages 6-12
February 23, 2019 - News study reanalyzes the effects of noncaloric sweeteners on gut microbiota
February 23, 2019 - New device allows scientists to reproduce blow effects on the heart in lab
February 23, 2019 - Holy herb identified as a potential treatment for Alzheimer’s disease
February 23, 2019 - New technology platform digitally counts growth factors in single cells
February 23, 2019 - Surgery and other treatments offer viable options for adult scoliosis
February 23, 2019 - Reduced antibody adaptability may make the elderly more vulnerable to influenza
February 23, 2019 - Neighborhood income, education associated with risk of disability progression in MS patients
February 23, 2019 - Endocrine Society opposes new rule that restricts access to Title X Family Planning Program
February 23, 2019 - 2019 guidelines for management of patients with atrial fibrillation
February 23, 2019 - Surprise rheumatoid arthritis discovery points to new treatment for joint inflammation
February 23, 2019 - A just-right fix for a tiny heart
February 23, 2019 - UMass Amherst scientist explores role of citrus peel in decreasing gut inflammation
February 23, 2019 - Owlstone Medical and Shanghai Renji Hospital collaborate to initiate breath biopsy lung cancer trial
February 23, 2019 - AMSBIO’s comprehensive portfolio of knock-out cell lines and lysates
February 23, 2019 - New app reliably determines physicians’ skills in forming accurate, efficient diagnoses
February 23, 2019 - Peripheral nerve injury can trigger the onset and spread of ALS, shows study
February 23, 2019 - Researchers uncover mechanisms that prevent tooth replacement in mice
February 23, 2019 - Once-a-day capsule offers new way to reduce symptoms of chronic breathlessness
February 23, 2019 - FDA Adds Boxed Warning for Increased Risk of Death with Gout Medicine Uloric (febuxostat)
February 23, 2019 - Phone-based intervention aids rheumatoid arthritis care
February 23, 2019 - Opioid epidemic makes eastern inroads and targets African-Americans
February 23, 2019 - New identified biomarker predicts patients who might benefit from HER2-targeted agents
February 23, 2019 - Study offers new insights into mechanisms of changes in erythrocytes under stress
February 23, 2019 - Antipsychotic polypharmacy may be beneficial for schizophrenia patients
February 23, 2019 - Researchers investigate how marijuana and tobacco co-use affects quit attempts by smokers
February 23, 2019 - Patients with diabetes mellitus have high risk of stable ischemic heart disease
February 23, 2019 - Transparency on healthcare prices played key role in Arizona health system’s turnaround
February 23, 2019 - A comprehensive, multinational review of peppers around the world
February 23, 2019 - Study finds modest decrease in burnout among physicians
February 23, 2019 - A simple change can drastically reduce unnecessary tests for urinary tract infections
February 23, 2019 - Deep Learning-Enhanced Device Detects Diabetic Retinopathy
February 23, 2019 - Researchers discover new binding partner for amyloid precursor protein
February 23, 2019 - Modest decrease seen in burnout among physicians, researchers say | News Center
February 23, 2019 - Transplanting bone marrow of young mice into old mice prevents cognitive decline
February 23, 2019 - Mogrify to accelerate novel IP and cell therapies using $3.7m USD funding
February 23, 2019 - Johns Hopkins study describes cells that may help speed bone repair
February 23, 2019 - Scientists demonstrate influence of food odors on proteostasis
February 23, 2019 - Researchers unlock the secret behind reproduction of fish called ‘Mary’
February 23, 2019 - Acupuncture Could Help Ease Menopausal Symptoms
February 23, 2019 - Researchers use AI to detect early signs of Alzheimer’s
February 23, 2019 - On recovery, vulnerability and ritual: An exhibit in white | News Center
February 23, 2019 - Memory Stored in Unexpected Region of the Brain
February 23, 2019 - Several health experts worldwide gather at EUDONORGAN event
February 23, 2019 - Discovery of potent compound in native California shrub may lead to treatment for Alzheimer’s
February 22, 2019 - Researchers create new map of the brain’s own immune system
February 22, 2019 - ICHE’s reviews on surgical infections, unnecessary urine tests, and nurses’ role in antibiotic stewardship
February 22, 2019 - UK Research and Innovation invests £200 million to create new generation of AI leaders
February 22, 2019 - Takeda collaboration to boost fight against Alzheimer’s and other neurodegenerative diseases
February 22, 2019 - Heavy drinking may change DNA, leading to increased craving for alcohol
February 22, 2019 - U.S. opioid deaths jump fourfold in 20 years; epidemic shifts to Eastern states | News Center
February 22, 2019 - 5 Questions with William Turner on Diversity in Medicine
February 22, 2019 - HHS Finalizes Rule Seeking To Expel Planned Parenthood From Family Planning Program
February 22, 2019 - Researchers uncover biochemical pathway that may help identify drugs to treat Alzheimer’s
February 22, 2019 - Biologist uses new grant to find ways to eliminate schistosomiasis
February 22, 2019 - Bag-mask ventilation to help patients breathe during intubation prevents complications
February 22, 2019 - AbbVie Announces New Drug Application Accepted for Priority Review by FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis
February 22, 2019 - Nature versus nurture and addiction
February 22, 2019 - New website connects researchers with data experts, resources | News Center
February 22, 2019 - Today’s Concerns About Drug Prices Echo The Past
February 22, 2019 - CT and Doppler equipment have low accuracy in detecting cerebral vasospasm and ischemia
February 22, 2019 - Study finds out similarity in function between healthy retina cell and tumor cell
How do metastatic tumor cells grow in lymph nodes?

How do metastatic tumor cells grow in lymph nodes?

image_pdfDownload PDFimage_print
How do metastatic tumor cells grow in lymph nodes?
(Left) Schematic diagram for the mechanism of tumor lymph node metastasis.

(Right) (A) Stepwise growing metastatic melanoma in tumor-draining lymph node and (B) fatty acid oxidation inhibitor, Exomoxir, suppresses lymph node metastasisCancer cells adapt to a challenging lymph node environment through YAP-dependent adjustment to fatty acid oxidation and usage of the plentiful fatty acids as fuel. Highly accumulated bile acids are potential molecular triggers of YAP activation that act mainly through vitamin D receptor (VDR) in metastatic lymph nodes. (A) Immunofluorescence images showing normal naïve lymph node (LN) and GFP+ tumors (green) in micro- and macro-metastatic lymph node of primary GFP+ melanoma bearing mice. The researchers conducted a comparative mRNA analysis in tumor cells growing in primary site (primary tumor) versus in micro- and macro-metastatic lymph nodes. As a result, the researchers uncovered the genes that regulate fatty acid metabolism are up-regulated in the metastatic tumor cells. (B) Comparison of metastatic lymph node between control- and etomoxir-treated groups. Metastatic melanoma (black-pigmented cells) in lymph node is rarely found in etomoxir-treated group, it is mostly found in control vehicle-treated group. Credit: IBS

The spread of cancer to a new part of the body accounts for about 90 percent of cancer deaths. Cancer cells can spread from sites of origin to other parts of the body through blood vessels (blood-borne metastasis) or the lymphatic system (LN metastasis). By invading surrounding lymph vessels, cancer cells migrate to adjacent lymph nodes and become a colonized tumor, leading their way to other organs. If they adapt and grow in lymph nodes, the cancer cells can easily reach other organs, resulting in a worse outlook for patient’s survival.

Medical oncologist Dr. Choong-kun Lee, cancer biologist Dr. Gou Young Koh, and their colleagues at the Center for Vascular Research within the Institute for Basic Science (IBS) and Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, South Korea, have revealed a mechanism to suppress the growth and spread of cancer cells in lymph nodes, forestalling any chance for them to invade new territories of the body.

Lymph nodes are tiny structures that contain immune cells to fight harmful substances such as cancer. Despite the underlying mechanism of immunity, cancer cells can adapt and grow in lymph nodes. This lymph node metastasis status is critical in cancer staging and prognosis. IBS researchers hypothesized that the migrated cancer cells must have an alternative mechanism to survive and grow in lymph nodes, which is different from where they begin.

The researchers used animal models with melanoma and breast cancer, which are considered to be most likely to spread first to lymph nodes. With the comparison of cancer cells grown in lymph nodes with those grown in the primary site, the researchers found that the metastatic cancer cells in lymph nodes boost the expression of the genes related to breaking down fatty acids to produce energy in a process known as fatty acid oxidation (FAO).

In the meantime, the cancer cells growing at primary site promote the expression of the genes involved in glucose used as an energy source (the well-known “Warburg” effect). In addition, they also found that unlike other organs, lymph nodes are rich with a variety of lipids. Dr. Lee says, “These unexpected results gave me strong confidence that lymph node metastatic tumor cells preferentially use fatty acids rather than glucose as a fuel source in the lipid-rich lymph node microenvironment.” He confirmed the findings with the almost complete suppression of lymph node metastasis by treating a clinically tested fatty acid oxidation inhibitor to melanoma or breast cancer-bearing mice.

How do metastatic tumor cells grow in lymph nodes?
Immunofluorescence images showing YAP activation (green) in metastatic melanoma (A) and breast cancer (B) in the tumor-draining lymph node. The researchers unveiled that this activated YAP is a crucial driver of tumor lymph node metastasis by stimulating fatty acid oxidation. Credit: IBS

The researchers sought to find the intracellular signal responsible for triggering such a metabolic adaptation for the metastatic tumor cells to use fatty acid as fuel. Using extensive screening and analyses, they identified yes-associated protein (YAP) as a crucial driver molecule for stimulating fatty acid oxidation in the metastatic tumor cells at lymph nodes. Dr. Koh says, “We were lucky to find a link between this unusual metabolic adaptation and YAP activation in the lymph node metastatic cancer cells. YAP activation was also found in the metastatic lymph nodes of patients with melanoma.”

To find out the major stimulator for YAP activation in lymph node metastatic tumors, the researchers looked into biological samples. They found that the abundance of several bile acid species—known to be detected only in the liver and intestinal tract, where they facilitate dietary fat digestion, was strikingly elevated in the lymph node metastatic melanoma.

Dr. Lee says, “It was a very intriguing that bile acids are highly accumulated in the metastatic lymph node, but not in the normal healthy lymph node or primary tumor.” The preliminary analyses suggest the lymph node metastatic tumor itself may produce bile acids that can activate YAP and stimulate further growth of the lymph node metastatic tumor. “It requires further extensive verification. Bile acids from blood and lymphatic circulation can be highly accumulated in lymph nodes during metastasis by a certain mechanism,” Dr. Koh says.

Cancer cells are smarter than expected in their dissemination in the body. Dr. Koh says, “This study reveals how they adapt to a challenging environment like lymph nodes by switching their energy source to locally abundant molecules such as fatty acids and bile acids to make their way to other organs.” Therapies targeting FAO and YAP are currently available or being actively developed. By drawing on the link between FAO /YAP and lymph node metastasis found by this study, doctors may be able to suppress subsequent distant metastasis in patients with melanoma and breast cancers. Dr. Koh adds, “It definitely warrants more extensive investigations in patients with metastatic cancers prior to clinical applications.”

The results are published in Science.

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

More information:
“Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation” Science (2019). … 1126/science.aav0173

Provided by
Institute for Basic Science

How do metastatic tumor cells grow in lymph nodes? (2019, February 7)
retrieved 9 February 2019

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Tagged with:

About author

Related Articles