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Distinctive field effects of smoking and lung cancer case-control status on bronchial basal cell growth and signaling.
Zefi, Olsida; Waldman, Spencer; Marsh, Ava; Shi, Miao Kevin; Sonbolian, Yosef; Khulan, Batbayar; Siddiqui, Taha; Desai, Aditi; Patel, Dhruv; Okorozo, Aham; Khader, Samer; Dobkin, Jay; Sadoughi, Ali; Shah, Chirag; Spivack, Simon; Peter, Yakov.
Afiliación
  • Zefi O; Department of Biology, Lander College, Touro University, New York, NY, 11367, USA.
  • Waldman S; Biology and Anatomy, New York Medical College, 10595, Valhalla, NY, USA.
  • Marsh A; Department of Biology, Lander College, Touro University, New York, NY, 11367, USA.
  • Shi MK; Biology and Anatomy, New York Medical College, 10595, Valhalla, NY, USA.
  • Sonbolian Y; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Khulan B; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Siddiqui T; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Desai A; Department of Biology, Lander College, Touro University, New York, NY, 11367, USA.
  • Patel D; Biology and Anatomy, New York Medical College, 10595, Valhalla, NY, USA.
  • Okorozo A; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Khader S; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Dobkin J; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Sadoughi A; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Shah C; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Spivack S; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Peter Y; Pulmonary Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Respir Res ; 25(1): 317, 2024 Aug 19.
Article en En | MEDLINE | ID: mdl-39160511
ABSTRACT
RATIONAL Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial "field" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases).

METHODS:

Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot.

RESULTS:

(a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs.

CONCLUSIONS:

These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bronquios / Transducción de Señal / Fumar / Proliferación Celular / Neoplasias Pulmonares Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Respir Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bronquios / Transducción de Señal / Fumar / Proliferación Celular / Neoplasias Pulmonares Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Respir Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos