Unexpected protein partnership has implications for cancer treatment

April 15, 2014

Scientists have identified two unlikely partners, in a type of immune cell called a macrophage, that work together, in response to cancer drugs, to increase inflammation in a way that may alter tumor growth. Researchers from the National Institutes of Health published the study in the journal Cancer Research.

These partners are the protein that suppresses tumors and the nuclear factor-kappaB (NF-kappaB) protein that stimulates their growth. Blocking this partnership could help prevent from occurring in cancer patients undergoing chemotherapy.

"Since many chemotherapy drugs target p53 to fight cancer cells, our finding helps us better understand the inflammatory-based side effects often seen in patients undergoing chemotherapy, as well as roles for inflammation within tumors," said Julie Lowe, Ph.D., lead author on the paper and fellow in the Laboratory of Respiratory Biology at the National Institute of Environmental Health Sciences (NIEHS), part of NIH.

Both p53 and NF-kappaB have been studied in modern cancer research. But, until now, they have generally been viewed as having opposite effects on growth. This study is among the first to show a cooperative interaction between p53 and NF-kappaB in human , and to reveal unexpected roles of p53 in tumor-related macrophages.

The study described a new collaboration between two major pathways to generate inflammation, said Michael Resnick, Ph.D., senior author and head of the NIEHS Chromosome Stability Group.

Inflammatory responses to exposures of p53-activating chemotherapeutic drugs were measured in immune cells from the blood and lungs of healthy volunteers at the NIEHS Clinical Research Unit. The researchers found that these drugs enhanced the expression of molecules that direct inflammation, an effect that required both p53 and NF-kappaB. The study also characterized a role for p53 in immune cells associated with tumors.

Currently, most cancer therapies related to the p53 tumor suppression process are directed at activating the . However, this study has clinical applications not only for cancer, but also for smoking-related lung disease. In both cases, p53 is activated in immune cells through chemotherapy, radiation, or smoking. Modifying this pathway through inhibitors of p53 activation could decrease the inflammatory response, both in cancer treatment and in lung diseases, such as chronic obstructive pulmonary disease.

Explore further: New study shows promise for preventing therapy resistance in tumor cells

More information: Lowe JM, Menendez D, Bushel PR, Shatz M, Kirk EL, Troester MA, Garantziotis S, Fessler MB, Resnick MA. 2014. p53 and NF-kappaB co-regulate pro-inflammatory gene responses in human macrophages. Cancer Res; DOI: 10.1158/0008-5472.CAN-13-1070 [Online 15 April 2014].

Related Stories

New study shows promise for preventing therapy resistance in tumor cells

January 9, 2014
A new study led by University of Kentucky researchers suggests that activating the tumor suppressor p53 in normal cells causes them to secrete Par-4, another potent tumor suppressor protein that induces cell death in cancer ...

p53 cuts off invading cancer cells

March 24, 2014
The tumor suppressor p53 does all it can to prevent oncogenes from transforming normal cells into tumor cells by killing defective cells or causing them to become inactive. Sometimes oncogenes manage to initiate tumor development ...

Cancer biologists link tumor suppressor gene to stem cells

March 26, 2014
Just as archeologists try to decipher ancient tablets to discern their meaning, UT Southwestern Medical Center cancer biologists are working to decode the purpose of an ancient gene considered one of the most important in ...

A gene family that suppresses prostate cancer

March 13, 2014
Cornell University researchers report they have discovered direct genetic evidence that a family of genes, called MicroRNA-34 (miR-34), are bona fide tumor suppressors.

Deficiency in p53 anti-tumor protein delays DNA repair after radiation

April 23, 2013
Researchers at Moffitt Cancer Center have found that a deficiency in an important anti-tumor protein, p53, can slow or delay DNA repair after radiation treatment. They suggest that this is because p53 regulates the expression ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

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.