Researchers find acidic pH microenvironments in tumours aid tumour cell survival
Tumour cell survival relies on adaptation to acidic conditions in the tumour microenvironment
- Date : 10 Sep 2012
- Topic : Basic science
Researchers at Moffitt Cancer Centre and colleagues at the University of South Florida and Wayne State University have discovered that tumour cell survival relies on adaptation to acidic conditions in the tumour 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 August 15 issue of Cancer Research.
Cancer progression is a multistep process strongly influenced by the physical properties of the tumour microenvironment. Both low oxygen and high acidity can be cytotoxic. According to Robert Gillies, PhD, corresponding author of the study and chair of Moffitt’s Department of Cancer Imaging and Metabolism, this research suggests that adaptation to these stressful conditions involves autophagy allowing cancer cells to survive, proliferate and eventually metastasise to secondary sites.
Learning more about autophagy and cellular adaptation
Not much is known about cell survival 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 tumour progression and potentially introduce novel therapeutic strategies, according to the researchers.
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.
They 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. According to Jonathan Wojtkowiak, a lead author of the study and postdoctoral fellow at Moffitt, a hallmark of cancer is the ability of cancer cells to evade apoptosis. Autophagy supports this by playing a tumour promoter and survival role under certain circumstances during different stages of tumourogenesis.
Theis 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 tumour 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.
Funding for the study came from the USA National Institutes of Health grants R01 CA077575, U54 CA143970 and R01 CA 131990.
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