Document Detail

Angiogenic switching in the alveolar capillaries in primary lung adenocarcinoma and squamous cell carcinoma.
MedLine Citation:
PMID:  17965528     Owner:  NLM     Status:  MEDLINE    
The status of angiogenic switching was examined in alveolar capillaries of primary lung adenocarcinoma (ADC) from 10 patients and primary squamous cell carcinoma (SCC) from 11 patients, using immunostaining for CD31, thrombomodulin, von Willebrand factor (vWF), collagen types IV and VII, and alpha-smooth muscle actin (alpha-SMA). We applied the TdT-mediated dUTP nick-end labeling assay and the reverse transcription-polymerase chain reaction for vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). In bronchioloalveolar and papillary subtypes of ADC, the neoplastic cells, replacing the normal alveolar epithelial cells, had spread over alveolar walls and adhered firmly to alveolar interstitium as shown by the development of type IV collagen. Neoplastic cells of SCC were characterized by local proliferation in alveolar sacs without firm attachment to alveolar walls. Tumor lesions of SCC had often developed necrotic foci of various size. In ADC and SCC, alveolar capillary endothelial cells newly obtained reactivity to vWF. Such segments of endothelial cells lost surface thrombomodulin expression. CD31 was consistently expressed in normal and ADC tissues, but each endothelial cell marker was often attenuated or even lost in SCC, suggesting degeneration or necrosis of the alveolar capillaries. The capillary pericytes and interstitial fibroblasts were often hypertrophic and developed alpha-SMA in the cytoplasm in ADC, but they became atrophic in SCC. In ADC, apoptosis occurred in cells of alveolar capillaries more frequently in the peripheral zone than in the deeper zone of the tumor, whereas the frequency was not consistent in SCC. In microdissected alveolar wall tissues, mRNA expression patterns of VEGF isoforms and VEGFRs were similar in both ADC and SCC. In ADC, de novo angiogenic switching took place in cytoplasm as a unit of cells segments in alveolar capillary endothelium. Suppression of angiogenic switching in SCC implies that factors other than VEGF-VEGFR interaction, such as physical contact and compression of tumor cells, might play a critical role in alveolar capillaries.
Chizuko Morishita; Enjing Jin; Mari Kikuchi; Seiko Egawa; Masakazu Fujiwara; Yoshiharu Ohaki; Mohammad Ghazizadeh; Tamiko Takemura; Oichi Kawanami
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of Nippon Medical School = Nippon Ika Daigaku zasshi     Volume:  74     ISSN:  1345-4676     ISO Abbreviation:  J Nippon Med Sch     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-29     Completed Date:  2007-12-28     Revised Date:  2012-09-25    
Medline Journal Info:
Nlm Unique ID:  100935589     Medline TA:  J Nippon Med Sch     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  344-54     Citation Subset:  IM    
Department of Molecular Pathology, Institute of Gerontology, Field of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, kanagawa, Japan.
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MeSH Terms
Adenocarcinoma / blood supply*
Antigens, CD31 / analysis
Capillaries / pathology
Carcinoma, Squamous Cell / blood supply*
Endothelial Cells / pathology
Lung Neoplasms / blood supply*
Middle Aged
Pulmonary Alveoli / blood supply*,  pathology
Receptors, Vascular Endothelial Growth Factor / analysis
Thrombomodulin / analysis
Tumor Markers, Biological / analysis
Vascular Endothelial Growth Factor A / analysis
von Willebrand Factor / analysis
Reg. No./Substance:
0/Antigens, CD31; 0/Thrombomodulin; 0/Tumor Markers, Biological; 0/Vascular Endothelial Growth Factor A; 0/von Willebrand Factor; EC, Vascular Endothelial Growth Factor

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