Antitumor Effect of Antibody Against a Serex-defined Antigen (Uoeh-lc-1) on Lung Cancer Xenotransplanted into Severe Combined Immunodeficiency Mice.
From: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Cancer research
- Publish Date: Sep 2007
- ISSN: 0008-5472
- Volume: 67
- Issue: 17
- Pages: 8351-7
- Medium: Print
- Language: English
- Citation (JAMA): Mizukami Makiko, Hanagiri Takeshi, Yasuda Manabu, et al. Antitumor Effect of Antibody Against a Serex-defined Antigen (Uoeh-lc-1) on Lung Cancer Xenotransplanted into Severe Combined Immunodeficiency Mice.. Cancer Res. Sep 2007;67:8351-7
Abstract
We previously reported the humoral immune response of tumor-infiltrating B lymphocytes in a lung cancer patient and 22 genes coding tumor-associated antigens identified using the serological identification of antigens by recombinant expression cloning method. In this study, we investigated one of these genes, designated University of Occupational and Environmental Health-Lung cancer antigen-1 (UOEH-LC-1), which has an extracellular domain. Quantitative reverse transcription-PCR revealed that UOEH-LC-1 was expressed ubiquitously in the normal tissues tested. However, it was overexpressed in 5 of 11 (45.5%) lung cancer cell lines and also in 9 of 15 (60%) lung cancer tissues compared with the paired normal lung tissues. A sequence analysis revealed that UOEH-LC-1 has a transmembrane domain. Flow cytometry analysis using a polyclonal antibody against UOEH-LC-1 revealed positive staining on lung cancer cell lines that were positive for expression of mRNA of UOEH-LC-1. Phage plaque assay showed the specific reactivity of anti-UOEH-LC-1 antibody against UOEH-LC-1 protein derived from the antigen encoding phage. By immunohistochemical staining with the anti-UOEH-LC-1 antibody, 7 of 28 (25.0%) lung cancer specimens showed positive staining on the cell surface. The administration of anti-UOEH-LC-1 antibody inhibited the growth of the UOEH-LC-1-positive tumors that were xenotransplanted into severe combined immunodeficiency mice. Complement-dependent cytotoxicity was one of the mechanisms to suppress the tumor growth. These results suggest that the antibody against UOEH-LC-1 therefore seems to have a promising therapeutic potential as a treatment for lung cancer.
Mesh Headings (Keywords): Adenocarcinoma, Animals, Antibodies, Neoplasm, Antibody-Dependent Cell Cytotoxicity, Antigens, Neoplasm, Cell Proliferation, Cytotoxicity Tests, Immunologic, Humans, Immunotherapy, Lung Neoplasms, Mice, Mice, SCID, Neoplasm Proteins, RNA, Messenger, Tumor Cells, Cultured, Xenograft Model Antitumor Assays
Check for Full Text / PubMed Unique Identifier (PMID): 17804751
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