Angiogeneis in the alveolar walls with neoplastic cell spreading of primary lung carcinomas
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概要
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The plasma membranes of alveolar capillary endothelium showed linear distribution of thrombomodulin (TM), but their cytoplasm was rarely reactive for von Willebrand factor (vWf), referring to TM-dominant pattern. The juxtaalveolar microvessels located along the borders between the alveolar- and connective tissue-zones showed mosaic-like pattern of distribution for these antigens. Especially, the pulmonary venules and peribronchial microvessels measuring up to 40 μm in diameter, demonstrated the expression of thrombomodulin along the plasma membrane, and that of vWf in the cytoplasm. The heterogeneous distribution pattern of these antigens suggests topographic difference in endothelial cell function to maintain coagulatory and anticoagulatory balance in the normal human lung. In primary lung adenocarcinoma, neovascularization often occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor-bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt-1), and proliferating markers (Ki-67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription polymerase chain reaction (RT-PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic-like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumorbearing alveolar walls showed significant expression of mRNA of VEGF_<165> and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor-associated VEGF_<165> and of KDR in the alveolar walls in primary lung adenocarcinoma.
- 日本組織細胞化学会の論文
著者
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Kawanami Oichi
Department Of Pathology Institute Of Gerontology Nippon Medical School
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Kawanami Oichi
Department Of Molecular Pathology Institute Of Gerontology Nippon Medical School
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