Dataset Information

Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells.

ABSTRACT: Tumors often contain a small subset of drug-resisting, self-renewing, and highly metastatic cells called tumor initiating cells or cancer stem cells (CSCs). To develop new approaches to detecting and targeting lung cancer CSCs, we applied an "unbiased" peptoid combinatorial cell screen to identify highly specific ligands that bind a CSC subpopulation of non-small cell lung cancer cells (defined by Aldefluor positivity), but not the remaining aldefluor negative cancer cells from the same preclinical model. One of the 'hit' peptoids bound to plectin, a structural protein, predominantly expressed intracellularly, but whose localization on the cell surface is linked to tumor invasion and metastasis. Our studies show both genotypic and phenotypic correlations between plectin and lung CSCs, as well as association of high plectin mRNA expression with poor patient survival in lung adenocarcinoma, potentially identifying plectin as a biomarker for lung CSCs.

SUBMITTER: Raymond AC

PROVIDER: S-EPMC6802198 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells.

Raymond Aaron C AC Gao Boning B Girard Luc L Minna John D JD Gomika Udugamasooriya D D

Scientific reports 20191018 1

Tumors often contain a small subset of drug-resisting, self-renewing, and highly metastatic cells called tumor initiating cells or cancer stem cells (CSCs). To develop new approaches to detecting and targeting lung cancer CSCs, we applied an "unbiased" peptoid combinatorial cell screen to identify highly specific ligands that bind a CSC subpopulation of non-small cell lung cancer cells (defined by Aldefluor positivity), but not the remaining aldefluor negative cancer cells from the same preclini ...[more]

PMID: 31628412

Similar Datasets

Project description:To identify potential new reagents and biomarkers for early lung cancer detection we combined the use of a novel preclinical isogenic model of human lung epithelial cells comparing non-malignant cells with those transformed to full malignancy using defined oncogenic changes and our on-bead two color (red and green stained cells) (OBTC) peptoid combinatorial screening methodology. The preclinical model used normal parent lung epithelial cells (HBEC3-KT, labeled with green dye) and isogenic fully malignant transformed derivatives (labeled with a red dye) via the sequential introduction of key genetic alterations of p53 knockdown, oncogenic KRAS and overexpression of cMYC (HBEC3p53, KRAS, cMYC). Using the unbiased OBTC screening approach, we tested 100,000 different peptoids and identified only one (named JM3A) that bound to the surface of the HBEC3p53, KRAS, cMYC cells (red cells) but not HBEC3-KT cells (green cells). Using the JM3A peptoid and proteomics, we identified the protein bound as vimentin using multiple validation approaches. These all confirmed the cell surface expression of vimentin (CSV) on transformed (HBEC3p53, KRAS, cMYC) but not on untransformed (HBEC3-KT) cells. JM3A coupled with fluorophores was able to detect and stain cell surface vimentin on very early stage lung cancers but not normal lung epithelial cells in a fashion comparable to that using anti-vimentin antibodies. We conclude: using a combined isogenic preclinical model of lung cancer and two color screening of a large peptoid library, we have identified differential expression of cell surface vimentin (CSV) after malignant transformation of lung epithelial cells, and developed a new peptoid reagent (JM3A) for detection of CSV which works well in staining of early stage NSCLCs. This new, highly specific, easy to prepare, CSV detecting JM3A peptoid provides an important new reagent for identifying cancer cells in early stage tumors as well as a resource for detection and isolating of CSV expressing circulating tumor cells.

Dataset Information

Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells.

Publications

Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets