Increased cell proliferation and decreased apoptosis characterize congenital cystic adenomatoid malformation of the lung

Cass, Darrell L.; Quinn, Theresa; Yang, Eunjin; Liechty, Kenneth W.; Crombleholme, Timothy M.; Flake, Alan W.; Adzick, N. Scott

doi:10.1016/s0022-3468(98)90528-0

Cited by 134 publications

(81 citation statements)

References 19 publications

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“…This result is in good agreement with studies that have described low and constant AIs in the developing rat [16] and human foetal lungs [15]. In accordance with results obtained from studies with rabbits [17], a shift was observed from more mesenchymal and endothelial to predominantly epithelial cell apoptosis at the transition from the canalicular to the terminal saccular stage (26th gestational week).…”

Section: Discussionsupporting

confidence: 92%

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Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

May¹,

Strobel²,

Preisshofen³

et al. 2004

European Respiratory Journal

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. ABSTRACT: Apoptosis and proliferation and the effect of exogenous surfactant on these processes were investigated in the lungs of mechanically ventilated/oxygen-treated preterm infants with respiratory distress syndrome and stillborn foetuses.Apoptotic and proliferation indices were determined in lung tissue sections from 27 ventilated/oxygen-treated preterm infants and 29 stillborn foetuses. The effect of exogenous surfactant on apoptosis and proliferation was studied in 16 ventilated preterm infants; 11 untreated infants served as control. Apoptotic and proliferating cells were identified by double labelling combining terminal deoxynucleotidyltransferasemediated deoxyuridine triphosphate nick end-labelling or Ki-67 with cell marker proteins. Pathways to cell death were explored by immunolabelling of cleaved caspases-3, -8 and -9.In the lungs of ventilated/oxygen-treated preterm infants, the numbers of apoptotic and proliferating cells increased significantly compared to the respective numbers in the lungs of stillborn foetuses. Apoptosis was detected in alveolar epithelial cells, whereas epithelial, endothelial and smooth muscle cells proliferated. Surfactant treatment reduced apoptosis induced by ventilation/oxygen-treatment; however, the decrease was not significant. Caspases-8 and -9 do not contribute to ventilation-induced apoptosis, whereas caspase-3 is involved.In conclusion, ventilation/oxygen-treatment induces epithelial cell apoptosis and proliferation of epithelial, endothelial and smooth muscle cells in the lungs of preterm infants. Apoptosis and proliferation are involved in several processes during embryonal and foetal life and play an important role in normal cell turnover and tissue development.Although they have been implicated as mechanisms of obtaining correct cell number, they are involved in pathological processes. In the lung, these processes can result from oxygen injury caused by high oxygen concentrations. However, oxygen therapy is often necessary for patients suffering from pulmonary diseases. This is particularly true for preterm infants and neonates suffering from respiratory distress syndrome (RDS), who require supraphysiological concentrations of oxygen to maintain adequate blood oxygen tensions.In animal models, it has been demonstrated that apoptosis is significantly increased in lungs exposed to hyperoxia [1][2][3]. In addition, it could be shown that hyperoxia induces increased expression of genes encoding apoptosis-promoting proteins [1,2]. Proliferation, however, ceases as a consequence of hyperoxia in cell culture experiments with alveolar epithelial cells, fibroblasts and tracheal smooth muscle cells [4][5][6].Exogenous surfactant therapy remains an established treatment of RDS. Recently, it has become increasingly obvious that exogenous surfactant preparations have significant effects on cell physiology and inflammatory processes in the lung comprising suppression of pro-inflammatory cytokines, superoxide production and regulation of the pulmonary host defence [7,8]. Ho...

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Section: Discussionsupporting

confidence: 92%

“…The PI was low and did not vary significantly during weeks 22-36 of gestation. In contrast, other investigators have described a gradual decrease in proliferation during late gestation in human lungs [15].…”

Section: Discussionmentioning

confidence: 73%

Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

May¹,

Strobel²,

Preisshofen³

et al. 2004

European Respiratory Journal

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“…␤-catenin binding to E-cadherin assists with linkage of E-cadherin to the actin cytoskeleton decreasing ␤-catenin regulation of Wnt gene expression and subsequent altered cellular behavior, cell fate, and differentiation (46,51). We are not aware of any information addressing ␤-catenin and Wnt signaling in BPS and CCAM, but the increased E-cadherin levels that we observed in these lung anomalies may be one of the mechanisms causing altered cell fate and cell differentiation, possibly through altered Wnt downstream signaling (10,39,51).…”

Section: Discussionmentioning

confidence: 78%

“…Furthermore, in developing lung, ␤ 1 -integrin signaling is important for migration of epithelial cells (17). These altered molecular signaling mechanisms may be partially responsible for the aberrant airway branching seen in BPS and CCAM lesions through altered ␣ 2 ␤ 1 -integrin signaling causing altered cell-cell adhesion and subsequent changes in epithelial cell migration and cell proliferation (10,39,52,64).…”

Section: Discussionmentioning

confidence: 99%

Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation

Volpe

Chung²,

Ulm³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Volpe MV, Chung E, Ulm JP, Gilchrist BF, Ralston S, Wang KT, Nielsen HC. Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation. Am J Physiol Lung Cell Mol Physiol 297: L143-L152, 2009. First published May 1, 2009 doi:10.1152/ajplung.90618.2008.-In many organs, integrins and cadherins are partly regulated by Hox genes, but their interactions in airway morphogenesis and congenital lung diseases are unknown. We previously showed that the Hox protein HoxB5 is abnormally increased in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), congenital lung lesions with abnormal airway branching. We now report on ␣ 2-, ␣3-, and ␤1-integrin and E-cadherin expression in normal human lung and in BPS and CCAM tissue previously shown to have abnormal HoxB5 expression and on the relationship of cell adhesion molecule expression to Hoxb5 regulation. ␣ 2-, ␣3-, and ␤ 1 -integrins and E-cadherin expression in normal human lung and BPS and CCAM were evaluated using Western blot and immunohistochemistry. Fetal mouse lung fibroblasts with Hoxb5-specific siRNA downregulation were evaluated for ␣ 2-integrin protein levels by Western blot. Compared with normal human lung, a previously undetected ␣ 2-integrin isoform potentially lacking essential cytoplasmic sequences was significantly increased in BPS and CCAM, and ␣ 2-integrin spatial and cellular expression was more intense. Ecadherin protein levels were also significantly increased, whereas ␣ 3 increased in CCAM compared with canalicular, but not with alveolar, stage lung. ␤ 1-integrin levels were unchanged. We conclude that in BPS and CCAM, altered ␣ 2-integrin cytoplasmic signaling contributes to abnormal cellular behavior in these lung lesions. Aberrant cell adhesion molecule and Hox protein regulation are likely part of the mechanism involved in the development of BPS and CCAM.

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“…displaces other thoracic structures. 8 The usual appearance on chest skiagram is mass containing air fi lled cysts. The other radiological signs include mediastinal shift, pleuraland pericardial effusions and pneumothorax.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary congenital cystic adenomatoid malformation involving upper lobe with successful surgical management

Garg¹,

Saheer²,

Hassan³

et al. 2011

IJMEDPH

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Increased cell proliferation and decreased apoptosis characterize congenital cystic adenomatoid malformation of the lung

Cited by 134 publications

References 19 publications

Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation

Pulmonary congenital cystic adenomatoid malformation involving upper lobe with successful surgical management

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