Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Autophagy Enables Tumor Cells to Thrive in an Acidic Environment

By LabMedica International staff writers
Posted on 19 Sep 2012
Tumor cells forced to live in a hypoxic and acidic microenvironment have developed molecular pathways that activate autophagic activity within the cancer cells and provide them with the survival advantage they require to grow and spread.

Autophagy is a self-degradative cellular process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Autophagy also plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria, endoplasmic reticulum and peroxisomes, as well as eliminating intracellular pathogens. Thus, autophagy is generally thought of as a survival mechanism, although its deregulation has been linked to nonapoptotic cell death. Autophagy can be either nonselective or selective in the removal of specific organelles, ribosomes and protein aggregates, although the mechanisms regulating aspects of selective autophagy are not fully understood.

Usually autophagy is thought to be a cancer preventative process, as in addition to elimination of intracellular aggregates and damaged organelles, autophagy promotes cellular senescence and cell surface antigen presentation, protects against genome instability, and prevents necrosis. These functions give it a key role in preventing diseases such as cancer, neurodegeneration, cardiomyopathy, diabetes, liver disease, autoimmune diseases, and infections.

Autophagy can also promote cancer cell survival, as has been described in a recent study conducted by investigators from the Moffitt Cancer Center (Tampa, FL, USA) and published in the August 15, 2012, issue of the journal Cancer Research.

To investigate how tumors adapt to an acidic environment they examined the effect of low pH (6.7) on human breast carcinoma cells. For this study they used the MDA-MB-231 human breast cancer cell line, which is highly invasive and metastatic both in vitro and in mouse models. Experiments were conducted under atmospheric oxygen so that all observations could be linked to acidosis and not confounded by oxygenation status.

The investigators detected elevated autophagic activity after acute and chronic exposure to acidosis, which promoted cell survival and continued proliferation similar to control cells. Pharmacological inhibition of autophagy resulted in reduced viability of cells grown at low pH. In vivo data showed spatial concordance between autophagic proteins and volumes expected to be acidic, and the expression of autophagic biomarkers was reversed with systemic buffers that raised tumor pH.

Although typically reported as an acute stress response, the data presented in this publication indicate that acid stress may lead to chronic maintenance of autophagy even during periods of adequate nutrient and oxygen supply. These results point toward a potential therapeutic strategy for treating tumors by using an autophagy inhibitor, one that does not affect cells under neutral conditions.

“Cancer progression is a multistep process strongly influenced by the physical properties of the tumor microenvironment,” said senior author Dr. Robert J. Gillies, director of imaging research at the Moffitt Cancer Center. “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.”

Related Links:
Moffitt Cancer Center



Gold Member
Flocked Fiber Swabs
Puritan® Patented HydraFlock®
Verification Panels for Assay Development & QC
Seroconversion Panels
New
Binocular Laboratory LED Illuminated Microscope
HumaScope Classic LED
New
Community-Acquired Pneumonia Test
RIDA UNITY CAP Bac
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get complete access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Molecular Diagnostics

view channel
Image: Researcher Kanta Horie places a sample in a mass spectrometer that measures protein levels in blood plasma and other fluids (Photo courtesy of WashU Medicine)

Highly Accurate Blood Test Diagnoses Alzheimer’s and Measures Dementia Progression

Several blood tests are currently available to assist doctors in diagnosing Alzheimer's disease in individuals experiencing cognitive symptoms. However, these tests do not provide insights into the clinical... Read more

Immunology

view channel
Image: The findings were based on patients from the ADAURA clinical trial of the targeted therapy osimertinib for patients with NSCLC with EGFR-activated mutations (Photo courtesy of YSM Multimedia Team)

Post-Treatment Blood Test Could Inform Future Cancer Therapy Decisions

In the ongoing advancement of personalized medicine, a new study has provided evidence supporting the use of a tool that detects cancer-derived molecules in the blood of lung cancer patients years after... Read more

Microbiology

view channel
Image: Schematic representation illustrating the key findings of the study (Photo courtesy of UNIST)

Breakthrough Diagnostic Technology Identifies Bacterial Infections with Almost 100% Accuracy within Three Hours

Rapid and precise identification of pathogenic microbes in patient samples is essential for the effective treatment of acute infectious diseases, such as sepsis. The fluorescence in situ hybridization... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.