Analysis of MUC4 mucin expression in lung carcinoma cells and its immunogenicity.
BACKGROUND
MUC4 has been cloned from tracheobronchial mucosa cDNA and reportedly is highly expressed in some human malignancies, including lung carcinoma. However, little is known about molecular and biologic characteristics. The authors analyzed expression levels of MUC4 mRNA and protein in lung carcinoma cells and analyzed the immunogenicity of this mucin.


METHODS
Nine cultured lung carcinoma cell lines and 29 tumor samples from patients with lung carcinoma were examined by Northern hybridization for MUC4 mRNA expression and by flow cytometry or an immunohistochemical staining for its protein expression. Sera from the patients were examined for their reactivity with MUC4 by enzyme-linked immunosorbent assay.


RESULTS
Forty-four percent of the cell lines and 72% of the tumor samples showed high levels of MUC4 mRNA expression. Although MUC4 protein was not detected in any live carcinoma cell lines by flow cytometry using rabbit antisera reactive with the MUC4 core, pretreatment with paraformaldehyde and sialidase resulted in successful detection of the protein in 50% of the cell lines. An immunohistochemical study revealed that 67% of the tumors exhibited MUC4 protein expression without any digestion. In 29% of the patients, high levels of anti-MUC4 immunoglobulin M or immunoglobulin G were detected.


CONCLUSIONS
MUC4 protein expression was elevated in lung carcinoma tissues because of the increase in its mRNA expression and deglycosylation on its core. This mucin is sufficiently immunogenic to elicit humoral and cellular immunity specific for MUC4 in patients with malignant disease. MUC4 is expected to be useful as a target antigen in immunotherapy for patients with carcinoma of the lung.
Hanaoka
J
J
Second Department of Surgery, Shiga University of Medical Science, Seta, Otsu, Japan.
Kontani
K
K
Sawai
S
S
Ichinose
M
M
Tezuka
N
N
Inoue
S
S
Fujino
S
S
Ohkubo
I
I
D014408:Biomarkers, Tumor / Q000032:analysis*; D015152:Blotting, Northern; D015139:Blotting, Southern; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D055264:Mucin-4; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C524658:MUC4 protein, human; D055264:Mucin-4; D009077:Mucins; D012333:RNA, Messenger