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Cancer's Frequent Spread To The Lungs Is Driven By Important Amino Acid
A new study has identified one of the reasons why cancer frequently spreads from elsewhere in the body to the lungs: an amino acid called aspartate. The findings improve our understanding of cancer and open the door to new treatments for metastatic disease.
Over half of the patients whose cancer spreads from its site of origin will develop metastases, or secondary tumors, in the lung. It's known that cancer cells are transported from one part of the body to the lungs via arteries and lymphatic vessels. What is less well known is why cancer cells find the lungs so attractive.
A new study by researchers from the Vlaams Instituut voor Biotechnologie (VIB)-KU Leuven Center for Cancer Biology (CCB), Belgium, has identified one reason lung metastases are so common: an amino acid called aspartate.
"We found high levels of aspartate in the lungs of mice and patients with breast cancer compared to mice and mice patients without cancer, which suggests that aspartate may be important for lung metastasis," said Ginevra Doglioni, a PhD student at the CCB and the study's lead author.
Aspartate plays important roles in the body, including in the lungs. As an amino acid, it's one of the building blocks of proteins, crucial to the structure and function of lung cells. Additionally, it's involved in energy production, pH level maintenance, and immune support, all of which are vital for healthy respiratory function.
Translation is the biological process where genetic information is used to build proteins. The following is a simplified account of how this occurs. DNA is transcribed into messenger RNA (mRNA). MRNA carries the genetic code to the ribosome, the cell's protein-making machinery. Ribosomes read the mRNA sequence, and as the ribosome moves along the mRNA, amino acids are linked together in the order specified, forming a growing protein chain. A change in the translational instructions, or program, results in the production of a different set of proteins that allow the growth of cancer cells.
Eukaryotic translation initiation factor 5A (eIF-5A) is a protein that helps cells efficiently make other proteins, playing a key role in two translation stages: initiation and elongation (helping ribosomes move along the mRNA and add amino acids to the protein chain). Specifically, eIF-5A helps when the ribosome encounters challenging parts of mRNA, which would otherwise cause the ribosome to stall. EIF-5A contains a unique amino acid called hypusine. Hypusine is essential to eIF-5A; without it, it can't assist the ribosome. The production of hypusine via a chemical reaction is called hypusination.
To investigate what promoted secondary cancer growth in the lungs, the researchers performed single-cell RNA sequencing of metastases growing in healthy lungs and in lungs primed with tumor-growth-promoting factors produced by breast cancer cells. The latter resulted in more aggressive metastatic disease.
The researchers observed that patients and mice with breast cancer had high concentrations of aspartate in their interstitial fluid, the fluid that fills the spaces between the air sacs and surrounding blood vessels in the lungs. They also found that lung aspartate activated the N-methyl-D-aspartate (NMDA) receptor on the surface of the cancer cells, which promoted eIF5A hypusination and an alternative translation program that resulted in increased aggressiveness in the metastases.
"This correlation emphasizes the relevance of the findings in a clinical context and suggests that aspartate signaling may be a common feature of cancer cell growing in the lung," said Professor Sarah-Maria Fendt, a principal investigator at the CCB and the study's corresponding author.
The researchers say that their findings have improved our understanding of cancer biology and opened the door to developing a new treatment for metastatic disease.
The study was published in the journal Nature.
Source: VIB-KU Leuven CCB via EurekAlert!
Where Colon Cancer Spreads
If you have advanced colon cancer, there's a chance the cancer may spread to other parts of your body. Over time, cells will break off from the original tumor. If they go into your lymphatic system, the cancer can spread to your lymph nodes. This can make your lymph nodes feel hard or swollen. It may also block lymph fluid from draining, causing the area to swell.If the cancer cells enter your bloodstream, they can spread to other parts of your body. The liver is the most common place that colon cancer spreads because the blood from your intestine flows directly to your liver as it returns to your heart. Once the cancer cells reach small blood vessels, they can invade the blood vessel walls and move into the nearby tissue. As the cancer cells grow, a small tumor forms. This causes new blood vessels to form, which feed the growing tumor.
If colon cancer spreads to liver, you may notice weight loss, yellowing skin, or pain on the right side of your belly. Besides the liver, colon cancer can also spread to the lungs. This is because there is a large amount of blood flowing to your lungs, which may carry cancer cells from the bowel. When the cancer spreads to your lungs, you may have shortness of breath, chest infections, or a cough that won't go away.
Another place colon cancer can spread is your peritoneum, the membrane that lines the inside of your belly and pelvis. For more information about how colon cancer can spread, talk to your doctor. ","publisher":"WebMD Video"} ]]>
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If you have advanced colon cancer, there's a chance the cancer may spread to other parts of your body. Over time, cells will break off from the original tumor. If they go into your lymphatic system, the cancer can spread to your lymph nodes. This can make your lymph nodes feel hard or swollen. It may also block lymph fluid from draining, causing the area to swell.If the cancer cells enter your bloodstream, they can spread to other parts of your body. The liver is the most common place that colon cancer spreads because the blood from your intestine flows directly to your liver as it returns to your heart. Once the cancer cells reach small blood vessels, they can invade the blood vessel walls and move into the nearby tissue. As the cancer cells grow, a small tumor forms. This causes new blood vessels to form, which feed the growing tumor.
If colon cancer spreads to liver, you may notice weight loss, yellowing skin, or pain on the right side of your belly. Besides the liver, colon cancer can also spread to the lungs. This is because there is a large amount of blood flowing to your lungs, which may carry cancer cells from the bowel. When the cancer spreads to your lungs, you may have shortness of breath, chest infections, or a cough that won't go away.
Another place colon cancer can spread is your peritoneum, the membrane that lines the inside of your belly and pelvis. For more information about how colon cancer can spread, talk to your doctor.
I Got Stage 4 Colon Cancer At 28 — I Wish I Hadn't Ignored These Symptoms
Five years after being diagnosed with stage 4 colorectal cancer at 28, Joe Faratzis is reflecting on the six red flags that signaled he was struggling with a serious disease.
"I put these symptoms off for months before finally going to get a colonoscopy," Faratzis admitted on TikTok. "Don't risk your life by waiting to see a doc. Early screening could save you and your family."
Joe Faratzis was diagnosed with colorectal cancer five years ago at the age of 28. Joe Faratzis / TikTok Faratzis revealed six concerning symptoms of colorectal cancer he ignored. TikTok/radiant14percentThe US Preventive Services Task Force updated its colorectal cancer screening guidelines in 2021 to lower the recommended age to start screening from 50 to 45 for adults at average risk.
A steady rise in rates of colorectal cancer among adults under 50 prompted the change. Experts urge seeing a health care provider right away, no matter your age, if you have any symptoms of colon cancer.
Faratzis told Self magazine that he began experiencing signs in 2019. The longtime TMZ producer was experiencing mild pain in his abdomen when bent over and shared his concerns with his primary care doctor, who ordered a CT scan. Faratzis confessed that he blew off the test, figuring it wasn't necessary.
Six months later, he noticed blood on his toilet paper — but again, he dismissed it as no big deal, assuming it was caused by hemorrhoids.
Faratzis says now that he thought he was "invincible," but admits he also didn't want to have to get an awkward digital rectal exam.
Finally, things got bad enough that he couldn't brush off his symptoms any longer.
"The big catalyst that motivated me to take my symptoms seriously occurred a few months later. I was sitting on the couch and I passed gas, looked down, and saw blood," explained Faratzis, now 34. "I went to the bathroom and there was about a half a cup of blood in the toilet. It wasn't painful, but I was like, 'Holy f–k — obviously there's some issue here.'"
"I put these symptoms off for months before finally going to get a colonoscopy," Faratzis said. "Don't risk your life by waiting to see a doc." TikTok/radiant14percentColorectal cancer develops in the tissues of the colon or rectum — both are part of the large intestine in the digestive system.
The disease is caused by changes in DNA, which can be inherited from parents or acquired later in life by consuming a low-fiber and high-fat Western diet, adopting a sedentary lifestyle, drinking a lot of alcohol and/or smoking.
It's the second leading cause of cancer-related deaths in the US, with the American Cancer Society estimating that about 53,000 Americans will die of colorectal cancer this year.
Early detection can improve survival chances. Treatment often involves surgery to remove the tumor, chemotherapy and radiation therapy.
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These are the six symptoms he wish he hadn't ignored:
"[One thing] that I should have paid more attention to is just noticing that I was going to the bathroom way more often than I should have, probably like a couple times a day," he said on TikTok.
Faratzis said he underwent oral and intravenous chemotherapy and procedures to remove the section of his colon containing cancer and burn and freeze lesions that developed on his lungs and liver.
"If I got the CT scan back in 2019 when I had my earliest colorectal cancer symptoms — I might not have wound up in the position I'm in now," Faratzis lamented to Self in March.
With chemo and other treatments, though, Faratzis' health improved, and in 2023 he got back his first clear CT scans. In April, he celebrated a year of clear scans.
His most recent one was last week. He noted: "I get to, I guess, kind of forget about this for another three months" — until his next scan.
Faratzis has been speaking out on social media to warn others about the signs they may be missing.
"Turns out, having a functioning rectum is actually really important for your quality of life," he said.
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