Inhibition of epidermal growth factor-like growth factor secretion in tracheobronchial epithelial cells by vitamin A

Lisa Miller, Ling Zhong Cheng, Reen Wu

Research output: Contribution to journalArticle

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Abstract

Vitamin A deficiency of respiratory tract epithelium results in the phenomenon of squamous cell metaplasia. The mechanisms by which vitamin A regulates airway epithelial cell growth and differentiation are not completely understood. In this study, we focused on the effects of vitamin A (retinol) on growth of human and non-human primate tracheobronchial epithelial (TBE) cells in culture. Retinol and its derivatives have little growth-stimulatory effect on TBE cells that are maintained in primary culture in a serum-free medium supplemented with 6 hormonal supple-ments: insulin, transferrin, epidermal growth factor (EGF), hydrocortisone, cholera toxin, and bovine hypothalamus extract. However, it was observed that retinol exhibited dose-dependent inhibition of TBE cell growth when EGF was removed from this serum-free culture condition. This inhibition can be reversed if EGF or the conditioned medium of primary TBE cells that are maintained in vitamin A-deficient condition is added. This type of EGF-retinol interacting phenomenon was not observed with the 5 remaining hormonal supplements. Analysis of 125I-labeled EGF binding shows a down-regulation of the high affinity binding sites (Kd = 0.09 nM) on TBE cells grown in the absence of vitamin A. These results suggest that TBE cells are capable of secreting an EGF-like growth factor in the absence of vitamin A. The possibility that transforming growth factor-α (TGF-α) is involved in this phenomenon is further examined by antibodies specific to TGF-α and its binding to an EGF-receptor. Using the TGF-α antibody, the presence of a TGF-α-specific antigen was found to be 3-fold higher in the conditioned medium obtained from the vitamin A-deficient cultures than that derived from retinol-treated cultures. Furthermore, the antibody neutralizing the TGF-α binding to an EGF receptor was able to reduce the DNA synthesis associated with the vitamin A deficiency. These results suggest that vitamin A plays an important regulatory role in the paracrine/autocrine secretion of EGF/TGF-α-like mitogen in TBE cell cultures.

Original languageEnglish (US)
Pages (from-to)2527-2533
Number of pages7
JournalCancer Research
Volume53
Issue number11
StatePublished - Jun 1 1993

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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