Human Tissue Distribution of TA02, Which is Homologous with a New Type of Aspartic Proteinase, Napsin A

Abstract

The N-terminal amino acid sequence of TA02 (molecular weight 35.0 kDa, isoelectric point 5.29), which is associated with primary lung adenocarcinoma, was determined and a fragment peptide was used to generate mouse monoclonal antibodies (mAbs) against TA02. The amino acid sequence suggested that TA02 might be homologous with napsin A, a new type of aspartic proteinase. In this context, we confirmed the expression of napsin A in primary lung adenocarcinoma using reversetranscription polymerare chain reaction (RT-PCR) and showed that the TA02 mAbs reacted with glutathione-S-transferase (GST)-napsin A fusion protein. We concluded that TA02 is the same molecule as napsin A, and showed immunohistochemically that it is distributed mainly in type II pneumocytes, alveolar macrophages, renal tubules and exocrine glands and ducts in the pancreas. In particular, type II pneumocytes and alveolar macrophages showed high expression of TA02 among human normal tissues. In primary lung adenocarcinoma, 47 out of 58 (81.0%) primary lesions were positive. All well-differentiated adenocarcinomas except those of goblet cell type showed high expression of TA02. In addition, two out of seven (28.6%) large cell carcinomas showed low expression of TA02. The other histopathological types of primary lung cancer did not express TA02 at all. A few cases of renal cell cancer, pancreatic cancer, breast cancer, thyroid cancer, colon cancer and ovarian cancer showed low expression, but the staining patterns were completely different from that of primary lung adenocarcinoma, which showed a granular staining pattern. Our novel mAbs should be valuable for immunochemical detection of TA02/napsin A.Key words: TA02 -napsin A -monoclonal antibody against TA02 -human aspartic proteinaseprimary lung adenocarcinoma Primary lung carcinoma incidence and mortality are still increasing. Even though primary lung carcinoma originates in bronchial epithelium, it shows a wide range of histopathological patterns. Adenocarcinoma accounts for approximately 40% of primary lung carcinoma in Japan. Most adenocarcinomas appear in peripheral bronchi. It is thought that this type of tumor originates from type II pneumocytes of the alveolar sac and Clara cells of the bronchiole. Other types of adenocarcinoma, which occur in relatively large bronchi, seem to derive from mucus cells, duct epithelial cells, goblet cells or bronchial glands. Based on the suspected cells of origin, primary lung adenocarcinoma can be subdivided into four types: type II pneumocyte type, Clara cell type, goblet cell type and bronchial gland type. 1)We have already reported the specific two-dimensional polyacrylamide gel electrophoresis patterns of each histological type of primary lung carcinoma.2) In that investigation we discovered TA02 polypeptide (TA02; molecular weight 35.0 kDa, isoelectric point 5.29), which is associated with primary lung adenocarcinoma.3) The intensity of TA02 expression reflected the degree of histopathological differentiation of primary lung adenocarcinoma, except for th...

Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma

“…High cytosolic cathepsin D levels are associated with poor prognosis in primary breast cancer (Foekens et al, 1999). Although we did not find an association between napsin expression and patients' prognosis in this study (data not shown), a correlation between napsin expression and the differentiation grade of adenocarcinoma was observed in accordance with previous reports (Hirano et al, 1997(Hirano et al, , 2000. The high positive rate (more than 80%) of napsin in lung adenocarcinoma and its close association with the differentiation grade may suggest a role of napsin in cancer development or differentiation.…”

“…Our group and another group have shown that napsin A is identical to the protein spots TAO1/TAO2 detected by two-dimensional gel electrophoresis of lung adenocarcinoma, and that napsin A is expressed in type II pneumocytes and lung adenocarcinomas (Chuman et al, 1999;Hirano et al, 2000). However, the detailed expression patterns of napsin A in association with other markers in lung cancer remain to be clarified.…”

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

“…[1][2][3][4] Napsin A has a role in processing pulmonary surfactant B protein produced by alveolar type II pneumocytes; 5,6 thus, it has been reported to be a good diagnostic marker for the confirmation of primary lung adenocarcinoma together with thyroid transcription factor 1 (TTF-1). [7][8][9][10][11][12][13] Expression of napsin A is also observed in the fetal kidney 14 and proximal tubules of the adult kidney, where it is most likely involved in protein catabolism.…”

Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker

“…We have applied this methodology to clinical materials of solid malignant neoplasm since 1992. [6][7][8] We detected some polypeptides related to drug resistance comparing 2-DE patterns of parent strains of lung cancer cultured cells with the CDDPresistant strains. We investigated the relationship between the expression of these polypeptides and its clinically postoperative effects of patients with NSCLC.…”