title: Carbonic anhydrase-related protein VIII increases invasiveness of non-small cell lung adenocarcinoma.
abstract: Carbonic anhydrase-related protein VIII (CA-RP VIII) is believed to be an oncofetal antigen and is overexpressed in colorectal and non-small cell lung cancer. However, the pathobiological properties of CA-RP VIII in lung cancer remain unclear. In the present study, we examined ultrastructural changes caused by exogenous CA-RP VIII expression in a well-differentiated lung adenocarcinoma cell line, PC-9. Many vacuoles lined by cilia, sometimes large vacuoles pushing the nuclei to one side, were found in the cytoplasm of CA-RP VIII-expressing PC-9 cells, but not in control PC-9 cells. Moreover, signet-ring cells containing abundant intracytoplasmic mucin were often found among CA-RP VIII-expressing PC-9 cells, but rarely among control PC-9 cells. We subsequently examined CA-RP VIII expression in atypical adenomatous hyperplasia and early-stage lung adenocarcinoma (Stage Ia). Significant expression of CA-RP VIII was observed in invasive lung adenocarcinoma but not in noninvasive adenocarcinoma. Interestingly, CA-RP VIII was strongly expressed in signet-ring cell cancer and invasive mucinous adenocarcinoma components. CA-RP VIII also appeared to enhance the invasiveness of PC-9 cells in Matrigel invasion assay. The present findings suggest that CA-RP VIII expression in lung adenocarcinoma is related to cancer cell invasion.
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Isao
authors.initials: I
authors.lastname: Nishimori
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Adachi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minakuchi
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sonobe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ohtsuki
authors.forename: Saburo
authors.initials: S
authors.lastname: Onishi
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000648:ultrastructure; D014408:Biomarkers, Tumor; D002256:Carbonic Anhydrases / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000648:ultrastructure*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000648:ultrastructure*; D046529:Microscopy, Electron, Transmission; D009077:Mucins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014617:Vacuoles / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins
chemical_list: D014408:Biomarkers, Tumor; D002256:Carbonic Anhydrases; D009077:Mucins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C512821:Car8 protein, mouse; C512818:CA8 protein, human; D047908:Intracellular Signaling Peptides and Proteins