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. 2011 Jul;59(7):701-10.
doi: 10.1369/0022155411410430. Epub 2011 May 6.

Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer therapeutic target

Lara P Stepan  1 , Esther S Trueblood, Kari Hale, John Babcook, Luis Borges, Claire L Sutherland
Affiliations

Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer therapeutic target

Lara P Stepan et al. J Histochem Cytochem. 2011 Jul.

Abstract

Trop2 is a cell-surface glycoprotein reported to be overexpressed in various types of adenocarcinomas with minimal expression in normal tissues. Recent findings that Trop2 expression correlates with tumor aggressiveness have increased interest in Trop2 as a potential target for cancer immunotherapy. The goal of this study was to extensively evaluate Trop2 expression at the transcript and protein levels in normal and tumor tissues. It was determined that Trop2 is overexpressed on some carcinomas relative to the corresponding normal tissue. However, in human and mouse, Trop2 is highly expressed at both the transcript and protein levels on several essential normal tissues. The findings suggest that the development of therapeutic agents to target Trop2 may require strategies that target Trop2 on malignant tissues in order to minimize potential toxicities to essential normal tissues that also express high levels of Trop2.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the authorship and publication of this article.

Figures

Figure 1.
Figure 1.
IHC analysis of human Trop2 protein expression. (A) Characterization of IHC antibody specificity. Left panel: MOv16 anti-human Trop2 monoclonal antibody detects bands corresponding to the predicted molecular weight of Trop2 in Western blots of untreated and deglycosylase-treated human Trop2-transduced 293T cells (lanes 2 and 3, respectively) but not parental 293T cells (lane 1). Right panel: MOv16 stains human and cynomolgus Trop2-transduced 293T cells but not human epithelial-specific cell adhesion molecule (EpCAM)-transduced or parental 293T cells. (B) Trop2 is highly expressed on human ovarian, colonic and thyroid carcinomas, but is not detected on the corresponding normal tissues.
Figure 2.
Figure 2.
Quantitative PCR analysis of Trop2 message expression in human and mouse. (A) Trop2 is overexpressed by human ovarian and intestinal tumors relative to the corresponding normal tissue. Expression for individual samples and means are shown. (B) Trop2 expression by normal human tissues. Trop2 expression from single patient samples (top panel) and from mRNA pooled from 10 or more patients per sample (bottom panel), relative to housekeeping gene, ACTB, is shown. The mean and standard deviation from triplicate samples are indicated. (C) Trop2 expression in normal murine tissues. The mean and standard deviation from triplicate samples are indicated.
Figure 3.
Figure 3.
Additional examples of human Trop2 protein expression. (A) Upper panel: Trop2 is highly expressed on many normal tissues including prostate, cervix, lung, breast, and uterus. Lower panel: Trop2 expression on the corresponding tumor tissues. (B) Additional examples of Trop2 expression in human kidney, thymus, skin, pancreas, and liver tissues. (C) High magnification images of selected normal and tumor tissues highlight the subcellular localization pattern of Trop2 staining.
Figure 4.
Figure 4.
IHC analysis of Trop2 protein expression in murine tissues and cynomolgus eye. (A) S-19F anti-murine Trop2 antibody stains murine Trop2-transduced but not parental 293T cells. (B) Trop2 protein is widely expressed by normal murine tissues. Examples of representative staining of cervix, lung, breast, uterus, salivary gland, kidney, thymus, skin, pancreas, and thyroid tissues are shown. (C) S-19F anti-Trop2 staining of murine eye (D) MOv16 anti-Trop2 staining of cynomolgus eye.
See this image and copyright information in PMC

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