Proteomic and ultrastructural analysis of Clara cell and type II alveolar epithelial cell-type lung cancer cells

Abstract

Background: Currently, the identification of Clara cell and type II alveolar epithelial cell-type cancer cells requires electron microscopy, which is a time-consuming and expensive process involving a complicated tissue sampling procedure. The aim of this study was to identify unique biomarkers for Clara cell and type II alveolar epithelial cell-type lung cancer cells, respectively, with proteomic profiling.Methods: Six human lung adenocarcinoma cell lines (A549, NCI-H358, NCI-H1650, HCC827, NCI-H1395, and NCI-H1975) were investigated for their ultrastructural characteristics. The differentially expressed proteins (DEPs) were screened between NCI-H358 cells (Clara cell type) and A549 cells (type II alveolar epithelial cell type) using two-dimensional difference gel electrophoresis (2D-DIGE) and matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS/MS), and then they were validated by western blot. The protein expression levels of endoplasmic reticulum oxidoreductin 1-α (ERO1L), Clara cell 10-kD protein (CC10), and surfactant protein C (SP-C) were also determined in the six cell lines assayed.Results: NCI-H358 cells featured Clara cell differentiation; A549, NCI-H1975, and HCC827 cells had characteristics of type II alveolar epithelial cells; and NCI-H1395 and NCI-H1650 cells had no differentiation characteristics of any lung adenocarcinoma cell type. Five DEPs including ubiquitin carboxylterminal hydrolase isozyme L1 (UCHL1), cytokeratin 19 (CK19), cytokeratin 8 (CK8), ERO1L, and peroxiredoxin 2 (PRDX2) between NCI-H358 and A549 cells were identified for further validation; however, none of them showed suitability as an effective biomarker. Similarly, CC10 and SP-C were not appropriate biomarkers.Conclusions: Cytological subtypes of NCI-H1975 and HCC827 cells were identified, but no promising biomarker was discovered in the present study.

MALDI-TOF MS: A Promising Analytical Approach to Cancer Diagnostics and Monitoring

“…Because of the late-stage diagnosis and the inadequate treatment choices, the survival rate is subpar, and as a result, screening for novel biomarkers is critical for the early detection of lung cancer. Hou et al [52] studied cell-type lung cancer cells proteome profile and observed that five differentially expressed proteins, including ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), cytokeratin 19 (CK19), cytokeratin 8 (CK8), ERO1L, and peroxiredoxin 2 (PRDX2), were significant between NCI-H358 and A549 cells. None of them demonstrated applicability as a reliable lung cancer biomarker.…”

Histological and ultrastructural studies on the effect of Cassia alata methanolic leaf extracts against chemically induced lung adenocarcinoma in rats

“…This conclusion was compatible with Reznik-Schuller (1976) who observed that long-term administration of nitrosamine derivatives to hamster rats, results in the production of bronchogenic carcinomas composed of neoplastic Clara cells. Tumor cells of the Clara cell type have a cluster of electrondense secretory granules, whereas tumor cells of the type II alveolar epithelial cell type have lamellar inclusion bodies inside the cytoplasm (Hou et al, 2020).…”