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Identification of ATP synthase beta subunit (ATPB) on the cell surface as a non-small cell lung cancer (NSCLC)

Ze-jun Lu1, Qi-fang Song, Sa-sa Jiang

  • 1Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, 37 Guoxue Xiang Street, Chengdu 610041, Sichuan, PR China. luzejun.01@163.com

BMC Cancer
|January 16, 2009
PubMed
Abstract

Insights

Researchers identified ATP synthase beta subunit (ATPB) as a novel lung cancer biomarker. This ectopically expressed protein on tumor cell membranes shows promise for non-small cell lung cancer (NSCLC) diagnosis and immunotherapy.

Area of Science:

  • Oncology
  • Immunotherapy
  • Biomarker Discovery

Background:

  • Antibody-based cancer immunotherapy shows promise but is limited by the scarcity of known tumor antigens.
  • Identifying novel, immunogenic antigens, particularly cell membrane markers, is crucial for advancing cancer diagnosis and therapy.

Purpose of the Study:

  • To identify novel tumor-associated antigens for non-small cell lung cancer (NSCLC) immunotherapy.
  • To develop a monoclonal antibody targeting a specific lung cancer antigen.
  • To evaluate the potential of the identified antigen as a diagnostic biomarker and therapeutic target.

Main Methods:

  • Immunization of mice with lung adenocarcinoma cell membrane proteins to generate monoclonal antibody 4E7 (McAb4E7).
  • Utilized hybridoma technique, MTT assay, flow cytometry, immunohistochemistry, Western blot, and proteomic technologies (2-DE, mass spectrometry) for antigen identification and validation.
  • Assessed McAb4E7's inhibitory effect on A549 cell proliferation.

Main Results:

  • Successfully produced McAb4E7 with inhibitory effects on A549 cell proliferation.
  • Identified ATP synthase beta subunit (ATPB) as the target antigen for McAb4E7 using proteomic analysis.
  • Confirmed ATPB's surface localization on A549 cells via flow cytometry.
  • Immunohistochemistry revealed aberrant ATPB expression in tumor cell membranes of NSCLC (adenocarcinoma and squamous carcinoma) but not in small cell lung cancer (SCLC), with high ectopic expression rates (71.88% and 66.67% respectively).

Conclusions:

  • Ectopic ATPB in the tumor cell membrane is identified as a non-small cell lung cancer (NSCLC)-associated antigen.
  • ATPB demonstrates potential as a biomarker for NSCLC diagnosis and a therapeutic target for NSCLC immunotherapy.

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