Navigation Links
Tumor cells engineer acidity to drive cell invasion, Moffitt Cancer Center researchers say
Date:1/24/2013

Researchers at Moffitt Cancer Center and colleagues at Wayne State University School of Medicine investigated the acidity in solid tumors to determine if pH levels play a role in cancer cell invasion in surrounding tissues. They found that an acidic microenvironment can drive cancer cells to spread and propose that neutralizing pH would inhibit further invasion, providing a therapeutic opportunity to slow the progression of cancers.

Their study appeared in the Jan. 3 online release of Cancer Research, a publication of the American Association for Cancer Research.

According to the study's corresponding author, Robert J. Gillies, Ph.D., chair of the Department of Cancer Imaging & Metabolism at Moffitt, acidity in solid tumors is the result of an increased fermentative metabolism combined with poor delivery of blood to tissues.

In this study, tumor invasion and pH were monitored in immunodeficient laboratory mice hosting a variety of tumors. "We monitored the test animals over time using microscopy and found that the highest regions of tumor invasion corresponded to areas with the lowest pH," Gillies explained. "Tumor invasion did not occur in regions with normal or near normal pH levels. Furthermore, when we neutralized the acidity with oral sodium bicarbonate, the invasion was halted."

Researchers proposed that the acidic pH of the tumor microenvironment represents a "niche engineering" strategy on the part of tumor cells, promoting invasion and growth of malignant tumors into surrounding tissue. Niche engineering is a concept in ecology describes how plants and animals alter their environment to in ways that promote their own growth and survival over their competitors. "We have long regarded cancers cells as an invading species," said study co-author Robert Gatenby, M.D., chair of the Diagnostic Imaging Services and Integrated Mathematical Oncology departments at Moffitt.

A key to this process of adaptation and invasion is increased glucose metabolism in the tumor. "The vast majority of malignant tumors metabolize glucose at high rates," Gillies said. "We have proposed that there is a direct, causative link between increased glucose metabolism and the ability of cancer cells to invade and metastasize."

According to the research, elevated glucose metabolism is the cause of increased acidity in the tumor microenvironment. Most tumors develop an abnormal vascular network that tends to be poorly organized and leaky, disrupting blood flow and hampering the delivery of oxygen.

"This poorly organized vascular system has a two-fold effect on tumor acidity," explained Gatenby. "First, it subjects tumor regions to poor perfusion, which restricts oxygen and increases the rate of glucose fermentation. Second, the poor perfusion hampers the ability to eliminate the resulting acids, resulting in very low pH in surrounding tissues."

As tumor cells adapt to increasing acidity, niche engineering through normal cell death and new blood vessel formation occurs in the tumor and the immune response is suppressed.

"Tumor cells perform niche engineering by creating an acidic environment that is not toxic to the malignant cells but, through its negative effects on normal cells and tissues, promotes local invasion of malignant cells," Gatenby said.

The researchers suggested that targeting this activity with buffers and other mechanisms aimed at increasing pH levels will likely provide a valuable alternative to traditional therapies focused entirely on killing tumor cells.


'/>"/>

Contact: Kim Polacek
kim.polacek@moffitt.org
813-745-7408
H. Lee Moffitt Cancer Center & Research Institute
Source:Eurekalert

Related medicine news :

1. Improved Stem Cell Line May Avoid Tumor Risk: Study
2. Normalizing tumor blood vessels improves delivery of only the smallest nanomedicines
3. Dental X-Rays May Be Linked to Benign Brain Tumors
4. Live imaging shows response to cancer drugs can be boosted by altering tumor microenvironment
5. Brain Tumor Vaccine Shows Promise in Early Trial
6. Kidney Cancer Patients Fare Better With Tumor Removal Only
7. IBN discovers human neural stem cells with tumor targeting ability
8. Protein prevents DNA damage in the developing brain and might serve as a tumor suppressor
9. Small molecular bodyguards kill HPV-infected cancer cells by protecting tumor-suppressor
10. New surgical technique for removing inoperable tumors of the abdomen
11. Combination of 2 drugs reverses liver tumors
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room , the ... Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. , “We ... new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice ...
(Date:6/25/2016)... ... , ... On Friday, June 10, Van Mitchell, Secretary of the Maryland Department ... in recognition of their exemplary accomplishments in worksite health promotion. , The Wellness at ... Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire was one of 42 ...
(Date:6/24/2016)... ... , ... Those who have experienced traumatic events may suffer from a complex ... as drug or alcohol abuse, as a coping mechanism. To avoid this pain and ... a traumatic event. , Trauma sufferers tend to feel a range of emotions, from ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary Hypertension ... that it will receive two significant new grants to support its work to ... its 25th anniversary by recognizing patients, medical professionals and scientists for their work ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, CA is ... Road To Recovery® program to drive cancer patients to and from their cancer treatments. ... the highest quality of life and ongoing independence. Getting to and from medical ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Mass. , June 24, 2016   Pulmatrix, ... pharmaceutical company developing innovative inhaled drugs, announced today that ... Russell Investments reconstituted its comprehensive set of ... "This is an important milestone for Pulmatrix," ... will increase shareholder awareness of our progress in developing ...
(Date:6/24/2016)... 24, 2016  Arkis BioSciences, a leading innovator ... more durable cerebrospinal fluid treatments, today announced it ... funding is led by Innova Memphis, followed by ... private investors.  Arkis, new financing will accelerate the ... market release of its in-licensed Endexo® technology. ...
(Date:6/23/2016)... June 23, 2016 Research and Markets ... Market - Forecast to 2022" report to their offering. ... method for the patients with kidney failure, it replaces the ... from the patient,s blood and thus the treatment helps to ... chloride in balance. Increasing number of ESRD ...
Breaking Medicine Technology: