Growth and differentiation of normal and transformed human bronchial epithelial cells

Masui, Tohru; Lechner, John F.; Yoakum, George H.; Willey, James C.; Harris, Curtis C.

doi:10.1002/jcp.1041290414

Cited by 22 publications

(9 citation statements)

References 63 publications

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“…It has been suggested that squamous metaplasia and dysplasia play an important role in lining epithelial cell transformation and that preneoplastic cells acquire a selective resistance to inducers of differentiation because the controlling pathways for the terminal aspects of this cellular process are defective. As a consequence, they may have a clonal growth advantage over normal cells (1)(2)(3)(4) and, in agreement with this hypothesis, diminished response to inducers of differentiation is a common characteristic of carcinomas (1,(5)(6)(7)(8)(9)(10)(11).…”

Section: Introductionsupporting

confidence: 61%

“…In our system, cholera toxin, a stimulator of intracellular cAMP, antagonizes the induction of terminal squamous differentiation by serum (48), which indicates a negative correlation between cAMP content and induction of differentiation. To test this hypothesis, we examined the effect of epinephrine, cholera toxin, and pertussis toxin on growth of NHBE cells exposed to TGF-p1.…”

Section: Role Of Camp In Squamous Differentiation Of Nhbe Cellsmentioning

confidence: 71%

“…In addition, the latent form of TGF-p1 is detected in conditioned medium of NHBE cultures (48). The isolation of a TGF-p1 binding protein (a2M) in serum has led to the speculation that secreted TGF-p1 is protected by formation of a TGF-pi-protein complex and released at target sites (49).…”

Section: Tgf-pl Induces Squamous Differentiationmentioning

confidence: 99%

“…None of the tumor cell lines underwent squamous differentiation induced by serum (7,48), TGFP3i (42), or TPA (64). Moreover, lung carcinoma cell lines are growth inhibited in serum-free medium, and growth is stimulated by serum, indicating that they acquired the ability to respond to unidentified growth factors in serum.…”

Section: Cigarette Smoke Condensate Induces Features Of Terminal Squamentioning

confidence: 99%

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Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

Pfeifer

Lechner

Masui

et al. 1989

Environ Health Perspect

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The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multidifferentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor PI (TGF-pi) and serum] and exogenous [e.g., 12-0-tetradecanoyl-13-phorbolacetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-PI or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (rs,ratfmyc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells.

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Section: Introductionsupporting

confidence: 61%

Section: Role Of Camp In Squamous Differentiation Of Nhbe Cellsmentioning

confidence: 71%

Section: Tgf-pl Induces Squamous Differentiationmentioning

confidence: 99%

Section: Cigarette Smoke Condensate Induces Features Of Terminal Squamentioning

confidence: 99%

See 2 more Smart Citations

Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

Pfeifer

Lechner

Masui

et al. 1989

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…However, chronic exposure to cigarette smoke can induce sustained production of TGF-and increased TGF-activation leading to expression of the 6 integrin, a TGF-responsive gene (Wang et al, 1996). This in turn contributes to a phenotypic switch from columnar ciliated to squamous epithelium (Masui et al, 1986a;Masui et al, 1986b). Squamous epithelial cells secrete increased amounts of IL-1 , which acts as a paracrine factor with adjacent airway fibroblasts to further activate TGF- (Araya et al, 2006), thereby increasing squamous metaplasia and further contributing to impaired barrier function and persistence of inhaled pathogens.…”

Section: Mucociliary Clearancementioning

confidence: 99%