Carcinoembryonic cell adhesion molecule 6 in human lung: Regulated expression of a multifunctional type II cell protein

Venkatadri Kolla, Linda W. Gonzales, Nicole A. Bailey, Ping Wang, Sreedevi Angampalli, Marye H. Godinez, Muniswamy Madesh, Philip L. Ballard

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycosylphosphatidylinositol (GPI)-anchored protein expressed in epithelial cells of various human tissues. It binds gram-negative bacteria and is overexpressed in cancers, where it is antiapoptotic and promotes metastases. To characterize CEACAM6 expression in developing lung, we cultured human fetal lung epithelial cells and examined responses to differentiation-promoting hormones, adenovirus expressing thyroid transcription factor-1 (TTF-1), and silencing of TTF-1 with small inhibitory RNA. Glucocorticoid and cAMP had additive stimulatory effects on CEACAM6 content, and combined treatment maximally increased transcription rate, mRNA, and protein ∼10-fold. Knockdown of TTF-1 reduced hormone induction of CEACAM6 by 80%, and expression of recombinant TTF-1 increased CEACAM6 in a dose-dependent fashion. CEACAM6 content of lung tissue increased during the third trimester and postnatally. By immunostaining, CEACAM6 was present in fetal type II cells, but not mesenchymal cells, and localized to both the plasma membrane and within surfactant-containing lamellar bodies. CEACAM6 was secreted from cultured type II cells and was present in both surfactant and supernatant fractions of infant tracheal aspirates. In functional studies, CEACAM6 reduced inhibition of surfactant surface properties by proteins in vitro and blocked apoptosis of electroporated cultured cells. We conclude that CEACAM6 in fetal lung epithelial cells is developmentally and hormonally regulated and a target protein for TTF-1. Because CEACAM6 acts as an antiapoptotic factor and stabilizes surfactant function, in addition to a putative role in innate defense against bacteria, we propose that it is a multifunctional alveolar protein.

Original languageEnglish (US)
Pages (from-to)L1019-L1030
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

Keywords

  • Adenosine 3′,5′-cyclic monophosphate
  • Alveolar type II cells
  • Apoptosis
  • Glucocorticoid
  • Surfactant
  • Thyroid transcription factor-1

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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