New Lung Cancer Stem Cell Biomarker Identified

New Lung Cancer Stem Cell Biomarker Identified

Researchers at the University of Houston have identified a new biomarker for lung cancer stem cells. Cancer stem cells (CSCs) or tumor-initiating cells (TICs) are cells that have similar abilities as standard stem cells. They can give rise to all cell types in a particular cancer. These CSCs are often present in tumors and populations can be drug resistant. Since the cells are self-renewing, they can cause relapse after treatment.

Most cancer treatments target the tumor rather than CSCs. Since the CDCs remain, they often give rise to new tumors. If treatments can be developed to target and kill these cells, the cancer can be treated, and relapse can be prevented.

Unfortunately, there are very few reliable biomarkers for CSCs. There are many possible biomarkers, including enzymes, hormones, and signaling molecules. These can vary from cancer to cancer and patient to patient. There is no single biomarker for CSCs, and there is no single drug that is effective at selectively attacking and killing CSCs.  These CSCs or TICs are responsible for 9 out of 10 cancer deaths.

With conventional therapy, non-stem cancer cells are killed but the stem cells remain and go on to form new tumors. If a CSC-specific therapy is developed, it will kill the CSCs and result in total regression.

The researchers looked at lung cancer CSCs and developed an “unbiased” peptoid combinatorial cell screen to identify ligands that bind to a CSC subpopulation of non-small lung cancer cells, but not to other types of cancer cells.

More than 400,000 synthetic peptoids were tested to see which captured the biomarker but did not bind to other cancer cells. Out of those 400,000 peptoids, three bound to cancer stem cells and not to other tumor cells.

The researchers identified one peptoid that bound to a structural protein called plectin, which is mostly expressed intracellularly. Its presence on the surface of cells has been linked to tumor invasion and metastasis. Studies have shown that high plectin mRNA expression is associated with poor lung adenocarcinoma survival rates.

Plectin helps with shaping cells and it plays an essential role in metastasis and spreading cells around the body. The researchers believe that plectin is a biomarker for lung cancer stem cells, and that it could be targeted with new drugs to prevent relapse and metastasis and that the peptoids could serve as potential therapeutics.

“In this study, we show that plectin is highly expressed on the surface of subpopulations of tumor cells within a panel of NSCLC cell lines. These plectin (+) subpopulations are highly clonogenic and enriched for cell migration and other properties of CSCs, and variably correlate with expression of previously described CSC markers such as ALDH1A3, CD44 and SOX2,” explained the researchers.

The study is detailed in the paper –Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells – which was recently published in Nature Scientific Reports. DOI: 10.1038/s41598-019-51004-3

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