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New Study Identifies Trigger That Turns Dormant Cancer Stem Cells Into Active Ones

DURHAM, N.C. FEBRUARY 26, 2020A new study released today in STEM CELLS identifies, for the first time, two morphologically and functionally different types of cancer stem cells found in cervical cancer. Of the two types, one exhibits an overexpression of cPLA2α, a key enzyme that triggers the transformation of dormant cancer stem cells into active ones, resulting in cervical cancer metastasis and recurrence. The information in this study could lead to new targets for treatments to halt tumor recurrence and metastatic spread. Also, it might accelerate the development of combination therapies.

The current standard of treatments for cervical cancer – the second leading cause of cancer death in young women worldwide — is radiotherapy and chemotherapy. However, the cancer’s resistance to chemotherapy and radiation, combined with a tendency to metastasis in the lymph nodes or recur in the pelvis, leaves doctors searching for more effective treatments.

Cervical cancer stem cells (CCSCs) are considered the major culprit behind the cancer’s ability to overcome these treatments. At the same time, a majority of cancer stem-like cells or tumor-initiating cells remain dormant. It takes a change in their microenvironment to spur them to metastasize.

“The mechanisms responsible for this must be identified to design more suitable therapies for the different subpopulations of cancer stem cells (CSCs) in various tissue-specific cancers,” said Hua Guo, Ph.D., who headed up the investigation along with Yuchao He, Ph.D. The two are colleagues at Tianjin Medical University Cancer Institute and Hospital. Researchers at Tianjin University of Traditional Chinese Medicine and at the Center for Translational Cancer Research, Peking University First Hospital, also participated in the study.

Although several cell surface antigens have been identified in CCSCs, these markers vary among tumors because of CSC heterogeneity. However, whether these markers specifically distinguish CCSCs with different functions is unclear. The study published in STEM CELLS sought to resolve this question. And in fact, its findings demonstrate that CCSCs exist in two biologically distinct phenotypes, characterized by different levels of cPLA2α expression.

“Our study showed for the first time that overexpression of cPLA2α results in a phenotype associated with mesenchymal traits, including increased invasive and migration abilities. On the other hand, CCSCs with cPLA2α downregulation show dormant epithelial characteristics,” said Dr. Guo. “In addition, cPLA2α regulates the reversible transition between mesenchymal and epithelial CCSC states through PKCζ, an atypical protein that governs cancer cell state changes.”

Dr. He added, “Now that we know cPLA2α triggers this transformation, we believe that cPLA2α might be an attractive therapeutic target for eradicating different states of CCSCs to eliminate tumors more effectively.”

“The novel study by Dr. Guo and team is of very high importance in understanding the transition between dormant cancer stem cells, which evade chemotherapy and radiation treatments, and actively dividing cells which can be better targeted, said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. “I applaud the group for this important discovery which will help researchers develop better treatments for cervical cancer.”

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The full article, “cPLA2α reversibly regulate different subsets of cancer stem cells transformation in cervical cancer,” can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3157.

Figure Caption: This study revealed that there are two morphologically and functionally distinct cancer stem cell populations regulated by cPLA2α in cervical cancer. cPLA2α might be a unique marker to identify different cancer stem cell populations and trigger quiescent epithelial cancer stem cells transform to invasive mesenchymal states. Overexpression of cPLA2α resulted in a CD44+CD24- phenotype with mesenchymal traits, whereas cervical cancer stem cells (CCSCs) with cPLA2α downregulation expressed CD133 and showed epithelial characteristics. cPLA2α, as a key role to reversely regulate CCSCs states and EMT, might provide innovative therapeutic strategies intended to halt tumor recurrence and metastasis.

About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST® (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

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