CD133, Trop-2 and alpha2beta1 integrin surface receptors as markers of putative human prostate cancer stem cells

Abstract

Cancer stem cells (CSCs) play a key role in initiation and development of cancer and are attractive targets for therapy. The identification of CSC surface receptors to be used as therapeutic targets in vivo remains a difficult task. In this study, we assessed the expression pattern of three surface receptors: CD133, Trop-2 and alpha2beta1 integrin in human prostate cancer in order to identify CSC-niches. CD133 was found to be expressed in small clusters of cells localized in focal areas of benign as well as malignant lesions, suggesting that this protein is a bona fide marker of the prostate stem/progenitor compartment. Trop-2 was localized in both basal and luminal layers of benign glands and was highly expressed in malignant lesions. Moreover, isolated cells in benign and malignant areas were found to co-express both CD133 and Trop-2. alpha2beta1 integrin was expressed in the prostatic epithelium as well as in the surrounding stroma, limiting its utility as a marker of CSCs. In summary, we demonstrate that the combination of CD133 and Trop-2 is useful to mark putative CSC-containing compartments in human prostate.

Keywords: CD133; Prostate cancer; Trop-2; cancer stem cells; immunohistochemistry; α2β1 integrin.

Figure 1

CD133 expression in benign and malignant prostate. CD133 immunostaining was performed using formalin-fixed, paraffin-embedded human PrCa sections. CD133 was detected (arrows) in isolated cells localized in the basal layer of benign prostate glands (left) or in small clusters in malignant areas (Gleason grade 4; right). Rabbit IgG, negative control.

Figure 2

Trop-2 expression in PrCa. Trop-2 immunostaining was performed using formalin-fixed, paraffin-embedded human PrCa sections. Trop-2 was found to be expressed at high levels in both benign (left) and malignant (Gleason grade 4; right) epithelial cells. Goat IgG, negative control.

Figure 3

Co-expression of Trop-2 and CD133 in putative CSC cells in PrCa. (A) Co-staining of Trop-2 and CD133 in benign (left) and malignant (right) areas. Double staining appears as dark red (arrows). Rabbit IgG and goat IgG, negative controls. (B) A benign gland is shown in the low-magnification panel, and a detail is shown in the high-magnification box. A cell co-expressing both Trop-2 and CD133 (arrow) appears distinguishable from cells expressing only CD133 or Trop-2 (arrowheads). Rabbit IgG and goat IgG, negative controls.

Figure 4

α2β1 integrin expression in PrCa. α2β1 integrin immunostaining was performed using sections from snap-frozen prostatic tumors. Expression of this protein was detected in epithelial cells of benign glands (arrows), and in the surrounding stroma (arrowheads). Mouse IgG, negative control.

Figure 5

p63 expression in benign and malignant prostate. p63 immunostaining was performed using formalin-fixed, paraffin-embedded PrCa sections to discriminate between benign and malignant areas. p63 showed nuclear localization in the basal cells of benign glands (A). p63 was undetectable in malignant lesions (Gleason grade 4; B) and selectively found in the nearby benign area (B, arrow). Mouse IgG, negative control.