論文 - 詳細
| RRC ID | 41781 |
|---|---|
| 著者 | Jin E, Fujiwara M, Pan X, Ghazizadeh M, Arai S, Ohaki Y, Kajiwara K, Takemura T, Kawanami O. |
| タイトル | Protease-activated receptor (PAR)-1 and PAR-2 participate in the cell growth of alveolar capillary endothelium in primary lung adenocarcinomas. |
| ジャーナル | Cancer |
| Abstract |
BACKGROUND:Cell growth can be induced via elicitation of protease-activated receptors (PAR) with serine proteases such as thrombin and trypsin. METHODS:To understand whether PAR are involved in tumor vessel formation in the neoplastic cell-bearing alveolar walls, immunohistochemical and reverse transcriptase-polymerase chain reaction analyses were performed using the lung tissues from 16 patients with primary lung adenocarcinomas. RESULTS:In microdissected tumor alveolar walls, the expressions of PAR-1 and PAR-2 mRNA were increased by 10-fold (P < 0.05) and 16-fold (P < 0.01), respectively, as compared with normal alveolar walls. Confocal microscopy revealed that tumor capillary endothelial cells in alveolar walls lost thrombomodulin expression. Instead, the expression of PAR-2 often became obvious at the normal border. Both PAR-1 and PAR-2 were expressed in the microvessel endothelial cells in tumors. Trypsin mRNA was expressed in 7 of the 16 cancer cell-bearing tissue specimens in contrast to 1 of the 14 normal alveolar walls. Immunohistochemically, trypsin was positive in the neoplastic cells from 10 patients and in lung adenocarcinoma cell lines (A549, HLC-1, LC-2, and PC-14). An in vitro assay showed a significant increase in idoxuridine (IdU) or bromodeoxyuridine uptake in human pulmonary artery endothelial cells and human umbilical cord vein endothelial cells after treatments with alpha-thrombin or activating peptides; SFLLRN for PAR-1 and SLIGKV for PAR-2, respectively. CONCLUSIONS:Thus, proliferation of alveolar capillary endothelial cells is initialized in part by PAR activation with serum thrombin and neoplastic cell-released trypsin. These results suggest a synergistic effect of PAR with vascular endothelial growth factor in alveolar angiogenesis. |
| 巻・号 | 97(3) |
| ページ | 703-13 |
| 公開日 | 2003-2-1 |
| DOI | 10.1002/cncr.11087 |
| PMID | 12548614 |
| MeSH | Adenocarcinoma / blood supply* Adenocarcinoma / metabolism Adenocarcinoma / pathology Capillaries / metabolism Capillaries / pathology Cell Division / drug effects Cell Division / genetics Endothelium, Vascular / metabolism Endothelium, Vascular / pathology Fluorescent Antibody Technique Humans Immunohistochemistry Lung Neoplasms / blood supply* Lung Neoplasms / metabolism Lung Neoplasms / pathology Microscopy, Confocal Neovascularization, Pathologic / genetics* Neovascularization, Pathologic / metabolism Oligopeptides / pharmacology Peptide Fragments / pharmacology Pulmonary Alveoli / blood supply* RNA, Messenger / analysis Receptor, PAR-1 Receptor, PAR-2 Receptors, Thrombin / genetics* Receptors, Thrombin / metabolism Reverse Transcriptase Polymerase Chain Reaction Thrombin / pharmacology Tumor Cells, Cultured |
| IF | 5.772 |
| 引用数 | 55 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) HLC-1(RCB0083) LC-2/ad(RCB0440) PC-14(RCB0446) |