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

1 Department of Pediatrics, Division of Newborn Medicine, Departments of 2 Pediatric Surgery and 3 Obstetrics and Gynecology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts Submitted 11 December 2008 ; accepted in final form 29 April 2009 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 β 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 β 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. E-cadherin protein levels were also significantly increased, whereas 3 increased in CCAM compared with canalicular, but not with alveolar, stage lung. β 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. 2 -integrin; 3 -integrin; E-cadherin; Hox proteins Address for reprint requests and other correspondence: M. V. Volpe, Dept. of Pediatrics, Division of Newborn Medicine, Tufts Medical Center, 750 Washington St., Box 44, Boston, MA 02111 (e-mail: mvolpe1{at}tuftsmedicalcenter.org )