Bladder expression of CD cell surface antigens and cell-type-specific transcriptomes

Abstract

Many cell types have no known functional attributes. In the bladder and prostate, basal epithelial and stromal cells appear similar in cytomorphology and share several cell surface markers. Their total gene expression (transcriptome) should provide a clear measure of the extent to which they are alike functionally. Since urologic stromal cells are known to mediate organ-specific tissue formation, these cells in cancers might exhibit aberrant gene expression affecting their function. For transcriptomes, cluster designation (CD) antigens have been identified for cell sorting. The sorted cell populations can be analyzed by DNA microarrays. Various bladder cell types have unique complements of CD molecules. CD9+ urothelial, CD104+ basal and CD13+ stromal cells of the lamina propria were therefore analyzed, as were CD9+ cancer and CD13+ cancer-associated stromal cells. The transcriptome datasets were compared by principal components analysis for relatedness between cell types; those with similarity in gene expression indicated similar function. Although bladder and prostate basal cells shared CD markers such as CD104, CD44 and CD49f, they differed in overall gene expression. Basal cells also lacked stem cell gene expression. The bladder luminal and stromal transcriptomes were distinct from their prostate counterparts. In bladder cancer, not only the urothelial but also the stromal cells showed gene expression alteration. The cancer process in both might thus involve defective stromal signaling. These cell-type transcriptomes provide a means to monitor in vitro models in which various CD-isolated cell types can be combined to study bladder differentiation and bladder tumor development based on cell-cell interaction.

Melphalan‐flufenamide is cytotoxic and potentiates treatment with chemotherapy and the Src inhibitor dasatinib in urothelial carcinoma

“…Interestingly, we found that the normally membrane-bound glycoprotein ANPEP was mainly confined to the cytoplasm of UC cells. The specific and, in most cases, abundant expression of ANPEP in UC cells which we here for the first time describe, noticeably illustrates activity of ANPEP in tumour and contrary not in the surrounding stromal cells as previous has been described (Goo et al, 2005;Liu et al, 2012). Taken together, the degree and proportion of ANPEP overexpression specifically in UC cells demonstrates activity of ANPEP and potentially a role in the development of this malignancy.…”

“…With respect to urinary bladder, ANPEP expression has been found in stroma cells of the superficial lamina propria, in the muscularis propria and in blood vessels (Goo et al., 2005). An altered expression of ANPEP in cells juxtapositioned to the superficial lamina propria has been demonstrated in UC, indicative of a cancer‐associated stromal component (Liu et al., 2012). The prognostic value of tumour ANPEP expression in UC patients treated by cystectomy remains scant.…”

Conversion of Prostate Adenocarcinoma to Small Cell Carcinoma‐Like by Reprogramming

“…The luminal‐like type included cancer cells of Gleason pattern 3, LNCaP, C4‐2, LuCaP 35 as they clustered around the luminal cell datapoint; the non‐luminal‐like type included cancer cells of Gleason pattern 4, CL1, DU145, PC3, LuCaP 49, as they clustered nearer the stem cell datapoints and distal to both the luminal and basal epithelial cell datapoints. The cancer cell types showed little expression signature of basal cells (also CD44 positive), which in turn showed little stem cell gene expression signature (Liu et al, ). The distance, a measure of relatedness, between datapoints, cell types A versus B, could be quantified by Δ = [(A 1 − B 1 ) 2 + (A 2 − B 2 ) 2 + (A 3 − B 3 ) 2 ] 1/2 with sub‐indices 1–3 representing the values in each coordinate along the three principal components axes.…”

Urothelial organoids originate from Cd49fHighstem cells and display Notch-dependent differentiation capacity

“…To define the cell-type of origin of the organoids, we isolated urothelial cell subpopulations. Immunofluorescence analysis of normal urothelium showed that CD49f selectively labels basal cells ( Figure 1A) (Liu et al, 2012). Purified CD49f high cells were enriched in basal markers whereas CD49f low cells were relatively enriched in luminal markers ( Figure 1D).…”