Samuel M. Cohen
[email protected]
0
0
Department of Pathology and Microbiology, University of Nebraska Medical Center
,
Omaha, NE 68198-3135
-
In reviewing the article by Wang et al. entitled, Reversal
and Prevention of Arsenic-Induced Human Bronchial
Epithelial Cell Malignant Transformation by MicroRNA-200b,
I became concerned regarding the pathology of the tumors
that grew in the nude mice upon transplantation of bronchial
epithelial cells transformed by arsenite in vitro. The
documentation of the pathology consists of a single, small photograph
which is difficult to interpret with regard to the histopathology.
Based on appearance, however, I am concerned that these tumors
do not represent bronchial epithelial malignancies, but rather,
either represent inflammatory tissue or mesenchymal
proliferation, either benign or malignant. Whether inflammation or
mesenchymal proliferation, neither would be indicative of an
effect that is representative of the kinds of tumors that occur in
humans in response to arsenic. The authors indicate that there is
epithelial to mesenchymal transformation in vitro, and they take
this as a sign of malignant transformation. However, in reality,
that is a late effect in malignant progression and usually is
associated with metastatic growth for lung tumors. The tumors in
humans that are induced by arsenic are all carcinomas. Lung
carcinomas in humans rarely have sarcomatoid (mesenchymal)
differentiation, which represent a rare subtype, and even in those
tumors epithelial differentiation is evident. More substantial
evidence should be provided by the authors that these truly
represent epithelial-derived tumors, either additional
histopathology or more definitively by a pankeratin
immunohistochemical stain. Without such documentation, the interpretation of this
article is misleading. If these are not carcinomas, the publication
would be more accurate to indicate that they have produced
epithelial to mesenchymal transformation but that this does not
necessarily imply carcinoma transformation in vitro by arsenite.
For comparison, in vitro transformation of urothelial cells by
trivalent arsenicals produced carcinomas when transplanted into
nude mice (Somji et al., 2006; Wnek et al., 2010).
A more limited issue that also needs to be addressed is that
this transformation in vitro is only occurring in p53-deficient
cells. This is similar to other in vitro models with arsenic, such
as those involving urothelial UROTsa cells that have been
reported by others (Somji et al., 2006; Wnek et al., 2010). In
contrast, individuals who develop tumors in response to arsenic
exposure are usually not p53 deficient nor are many of the
tumors that are induced.
Somji, S., Zhou, X. D., Garrett, S. H., Sens, M. A., and Sens, D. A. (2006).
Urothelial cells malignantly transformed by exposure to cadmium (Cd(2))
and arsenite (As(3)) have increased resistance to Cd(2) and
As(3)induced cell death. Toxicol. Sci. 94, 293301.
Wnek, S. M., Jensen, T. J., Severson, P. L., Futscher, B. W., and Gandolfi, A. J.
(2010). Monomethylarsonous acid produces irreversible events resulting in
malignant transformation of a human bladder cell line following 12 weeks of
low-level exposure. Toxicol. Sci. 116, 4457.
(...truncated)