Publication: The alveolar type II cell is a pluripotential stem cell in the genesis of human adenocarcinomas and squamous cell carcinomas
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Date
1997
Authors
Ten Have-pbroek, A.A.W. ; Benfield, J.R. ; Van Krieken, J.H.J.M. ; Dijkman, J.H.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Studies in a canine bronchogenic carcinoma
model indicate that alveolar type 11 cells may
differentiate from carcinogen-exposed epithelium of
larger bronchi and generate adenocarcinomas with
bronchioloalveolar and other growth patterns. In this
study, we investigated whether type 11 cells are one of
the major proliferating cells (=stem cells) in the genesis
of two major subsets of bronchogenic carcinoma in
humans. Adenocarcinomas (17 bronchioloalveolar; 3
papillary; and 10 other) and squamous cell carcinomas
(n=27) as well as (pre)neoplastic lesions in adjacent
bronchi and bronchioles were examined for the presence
of type 11 cell markers and cellular proliferation markers
(PCNA; Ki-67) using light and electron microscopy and
immunohistochemistry. Distinctive features of type 11
cells, which do not depend upon the degree of cell
maturity, are the approximately cuboid shape, large and
roundish nucleus, cytoplasmic staining for surfactant
protein A (SP-A), and presence of multilamellar bodies
or their precursory forms. Cells with this phenotype
were found in early progressive (i.e., dysplastic, in situ,
microinvasive) lesions in conducting airways and in al1
the carcinomas investigated, although with a much
greater abundance among glandular lesions compared to
squamous lesions. The most consistent sites of type 11
cells were the basal and adjacent epithelial layers.
Nuclear PCNA (Ki-67) expression usually predominated
in the same region. None of the lesions displayed
specific Clara cell features. Our findings strongly
suggest that the type 11 cell is a pluripotential stem cell
in human lung carcinogenesis. Based on our findings in
humans and dogs, we postulate that type 11 tumor stem
cells may originate from one of two sources: (1) normal
bronchial epithelium (by an oncofetal mechanism
of differentiation); and (2) normal alveolar type 11
cells.
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