Researchers find acidic pH microenvironments in tumors aid tumor cell survival

September 6, 2012

Researchers at Moffitt Cancer Center and colleagues at the University of South Florida and Wayne State University have discovered that tumor cell survival relies on adaptation to acidic conditions in the tumor microenvironment. Their research investigating the effects of acidity on breast and pancreatic cancer cell lines revealed the importance of autophagy in acidic microenvironments and suggests that a successful treatment strategy might be based on this autophagic dependence.

The study appears as the cover story for the Aug. 15 issue of Cancer Research, a publication of the American Association for Cancer Research.

" is a multistep process strongly influenced by the physical properties of the ," said Robert J. Gillies, Ph.D., corresponding author of the study and chair of Moffitt's Department of and Metabolism. "Both low oxygen and high acidity can be cytotoxic. Our research suggests that adaptation to these stressful conditions involves autophagy allowing cancer cells to survive, proliferate and eventually metastasize to secondary sites."

According to the authors, not much is known about mechanisms under acidic conditions, but it has been demonstrated that acidosis can alter gene expression leading to cell types that are adapted for growth and survival in low pH conditions. Identifying low pH survival mechanisms would "give further insight into and potentially introduce novel therapeutic strategies," researchers said.

In this study, the researchers tested cancer cell lines under acidic conditions to learn more about autophagy and cellular adaptation. They noted that normal cells in the acidic environment can respond to acidic stress by increasing cell death pathways, thus introducing the need for survival and adaptive mechanisms by cancer cells.

The researchers also noted that their experiments were carried out under atmospheric oxygen levels and they found that the cell's stress response could lead to chronic autophagy even when nutrients and oxygen were in adequate supply.

"We found that cells subjected to transient and chronic low pH growth conditions demonstrate elevated markers for autophagy and are dependent on this process for prolonged survival in acidic environments," explained Jonathan W. Wojtkowiak, lead author of the study and postdoctoral fellow at Moffitt. "A hallmark of cancer is the ability of to evade apoptosis. Autophagy supports this by playing a tumor promoter and survival role under certain circumstances during different stages of tumorogenesis."

Their study demonstrated the importance of autophagy in low pH-adapted breast and pancreatic cancer cell lines and the dependence of these cells on autophagy for survival to acidic tumor microenvironment. According to the researchers, they identified a potential therapeutic strategy of using an autophagy inhibitor, one that does not affect cells under neutral conditions.

Explore further: How aging normal cells fuel tumor growth and metastasis

More information: cancerres.aacrjournals.org/con … /72/16/3938.full.pdf

Funding for the study came from National Institutes of Health grants R01 CA077575, U54 CA143970 and R01 CA 131990.

Related Stories

How aging normal cells fuel tumor growth and metastasis

June 14, 2012
It has long been known that cancer is a disease of aging, but a molecular link between the two has remained elusive.

New combo of chemo and well-known malaria drug delivers double punch to tumors

February 19, 2012
Blocking autophagy -- the process of "self-eating" within cells -- is turning out to be a viable way to enhance the effectiveness of a wide variety of cancer treatments.

Specific inhibition of autophagy may represent a new concept for treatment of kidney cancer

April 16, 2012
New research at the University of Cincinnati (UC) suggests that kidney cancer growth depends on autophagy, a complex process that can provide cells with nutrients from intracellular sources. Researchers say in certain circumstances ...

Scientists discover mechanism that promotes lung cancer growth and survival

June 18, 2012
A multi-institutional research study has uncovered a new mechanism that may lead to unique treatments for lung cancer, one of the leading causes of death worldwide.

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

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.