Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Abbreviations

CB:

Bladder cancer

CD:

Cluster designation

EC:

Embryonal carcinoma

ES:

Embryonic stem

MACS:

Magnetic cell sorting

MIAME:

Minimum information about a microarray experiment

NB:

Normal bladder

PCA:

Principal components analysis

References

  1. Aaboe M, Marcussen N, Jensen KM, Thykjaer T, Dryskjøt L, Orntoft TF (2005) Gene expression profiling of noninvasive primary urothelial tumors using microarrays. Br J Cancer 93:1182–1190

  2. Aboseif S, El-Sakka A, Young P, Cunha G (1999) Mesenchymal reprogramming of adult human epithelial differentiation. Differentiation 65:113–118

  3. Bonkhoff H, Remberger K (1996) Differentiation pathways and histogenetic aspects of normal and abnoraml prostatic growth: a stem cell model. Prostate 28:98–106

  4. Choi YL, Lee SH, Kwon G, Park C, Han J, Choi JS, Choi HY, Kim S, Shin YK (2007) Overexpression of CD24, association with invasiveness in urothelial carcinoma of the bladder. Arch Pathol Lab Med 131:275–281

  5. Cunha GR, Alarid ET, Turner T, Donjacour AA, Boutin EL, Foster BA (1992) Normal and abnormal development of the male urogenital tract. Role of androgens, mesenchymal-epithelial interactions, and growth factors. J Androl 13:465–475

  6. Fleischmann A, Schlomm T, Huland H, Köllermann J, Simon P, Mirlacher M, Salomon G, Chun FHK, Steuber T, Simon R, Sauter G, Graefen M, Erbersdobler A (2008) Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients. Clin Cancer Res 14:7838–7842

  7. Goldstein AS, Huang J, Guo C, Garraway IP, Witte ON (2010) Identification of a cell of origin for human prostate cancer. Science 329:568–571

  8. Goo YA, Goodlett DR, Pascal LE, Worthington KD, Vessella RL, True LD, Liu AY (2005) Stromal mesenchyme cell genes of the human prostate and bladder. BMC Urol 5:17

  9. Hu P, Meyers S, Liang FX, Deng FM, Kachar B, Zeidel ML, Sun TT (2002) Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability. Am J Physiol Renal Physiol 283:F1200–F1207

  10. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264

  11. Kanematsu A, Yamamoto S, Ogawa O (2007) Changing concepts of bladder regeneration. Int J Urol 14:673–678

  12. Kristiansen G, Denhert C, Schluns K, Dahl E, Pilarsky C, Hauptmann S (2002) CD24 is expressed in ovarian cancer and is a new independent prognostic marker of patient survival. Am J Pathol 161:1215–1221

  13. Lee JH, Kim SH, Lee ES, Kim YS (2009) CD24 overexpression in cancer development and progression: a meta-analysis. Oncol Rep 22:1149–1156

  14. Li Y, Liu W, Hayward SW, Cunha GR, Baskin LS (2000) Plasticity of the urothelial phenotype: effects of gastrointestinal mesenchyme/stroma and implications for urinary tract reconstruction. Differentiation 66:126–135

  15. Liu AY, True LD (2002) Characterization of prostate cell types by CD cell surface molecules. Am J Pathol 160:37–43

  16. Liu AY, True LD, LaTray L, Nelson PS, Ellis WJ, Vessella RL, Lange PH, Hood L, Engh G van den (1997) Cell-cell interaction in prostate gene regulation and cytodifferentiation. Proc Natl Acad Sci USA 94:10705–10710

  17. Liu AY, Roudier MP, True LD (2004) Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile. Am J Pathol 165:1543–1556

  18. Marzolf B, Deutsch EW, Moss P, Campbell D, Johnson MH, Galitski T (2006) SBEAMS-Microarray: database software supporting genomic expression analyses for systems biology. BMC Bioinformatics 7:286

  19. Murali R, Delprado W (2005) CD10 immunohistochemical staining in urothelial neoplasms. Am J Clin Pathol 124:371–379

  20. Oottamasathien S, Wang Y, Williams K, Franco OE, Wills ML, Thomas JC, Saba K, Sharif-Afshar A, Makari JH, Bhowmick NA, DeMarco RT, Hipkens S, Magnuson M, Brock JW, Hayward SW, Pope JC, Matusik RJ (2007) Directed differentiation of embryonic stem cells into bladder tissue. Dev Biol 304:556–566

  21. Oudes AJ, Campbell DS, Sorensen CM, Walashek LS, True LD, Liu AY (2006) Transcriptomes of human prostate cells. BMC Genomics 7:92

  22. Pascal LE, Deutsch EW, Campbell DS, Korb M, True LD, Liu AY (2007) The urologic epithelial stem cell database (UESC)—a web tool for cell type-specific gene expression and immunohistochemistry images of the prostate and bladder. BMC Urol 7:19

  23. Pascal LE, True LD, Campbell DS, Deutsch EW, Risk M, Coleman IM, Eichner LJ, Nelson PS, Liu AY (2008) Correlation of mRNA and protein levels: cell type-specific gene expression of cluster designation antigens in the prostate. BMC Genomics 9:246

  24. Pascal LE, Goo YA, Vêncio RZN, Page LS, Chambers AA, Liebeskind ES, Takayama TK, True LD, Liu AY (2009a) Gene expression down-regulation in CD90+ prostate tumor-associated stromal cells involves potential organ-specific genes. BMC Cancer 9:317

  25. Pascal LE, Vêncio RZN, Goo YA, Page LS, Shadle CP, Liu AY (2009b) Temporal expression profiling of the effects of secreted factors from prostate stromal cells on embryonal carcinoma stem cells. Prostate 69:1353–1365

  26. Pascal LE, Vêncio RZN, Page LS, Liebeskind ES, Shadle CP, Troisch P, Marzolf B, True LD, Hood LE, Liu AY (2009c) Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes. BMC Cancer 9:452

  27. Pascal LE, Ai J, Vêncio RZN, Vêncio EF, Zhou Y, Page LS, True LD, Wang Z, Liu AY (2011a) Differential inductive signaling of CD90+ prostate cancer-associated fibroblasts compared to normal tissue stromal mesenchyme cells. Cancer Microenvironment 4:51–59

  28. Pascal LE, Vêncio RZN, Vessella RL, Ware CB, Vêncio EF, Denyer G, Liu AY (2011b) Lineage relationship of prostate cancer cell types based on gene expression. BMC Med Genomics 4:46

  29. Scriven SD, Booth C, Thomas DFM, Trejdosiewicz LK, Southgate J (1997) Reconstitution of human urothelium from monolayer cultures. J Urol 158:1147–1152

  30. Seiler R, Gunten M von, Thalmann GN, Fleischmann A (2012) High CD10 expression predicts favorable outcome in surgically treated lymph node-positive bladder cancer patients. Hum Pathol 43:269–275

  31. Sirchia SM, Tabano S, Monti L, Recalcati MP, Gariboldi M, Grati FR, Porta G, Finelli P, Radice P, Miozzo M (2009) Misbehaviour of XIST RNA in breast cancer cells. PLoS One 4:e5559

  32. Soto AM, Sonnenschein C (2011) The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory. Bioessays 33:332–340

  33. Staack A, Hayward SW, Baskin LS, Cunha GR (2005) Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration. Differentiation 73:121–133

  34. Taylor RA, Cowin PA, Cunha GR, Pera M, Trounson AO, Pedersen J, Risbridger GP (2006) Formation of human prostate tissue from embryonic stem cells. Nat Methods 3:179–181

  35. Vêncio RZ, Koide T (2005) HTself: self-self based statistical test for low replication microarray studies. DNA Res 12:211–214

  36. Vêncio EF, Pascal LE, Page LS, Denyer G, Wang AJ, Ruohola-Baker H, Zhang S, Wang K, Galas DJ, Liu AY (2011) Embryonal carcinoma cell induction of miRNA and mRNA changes in co-cultured prostate stromal fibromuscular cells. J Cell Physiol 226:1479–1488

  37. Ware CB, Nelson AM, Blau CA (2006) A comparison of NIH-approved human ESC lines. Stem Cells 24:2677–2684

Download references

Acknowledgments

We thank Pamela Troisch and Bruz Marzolf at the Institute for Systems Biology for array analysis, Susan Saiget for CD antibodies and Adam van Mason for specimen collection.

Author information

Correspondence to Alvin Y. Liu.

Additional information

Funding from the NCI Early Detection Research Network (CA111244 to A.Y.L.) and the NCI Pacific Northwest Prostate Cancer SPORE (P50CA097186) was used to support these studies.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Liu, A.Y., Vêncio, R.Z.N., Page, L.S. et al. Bladder expression of CD cell surface antigens and cell-type-specific transcriptomes. Cell Tissue Res 348, 589–600 (2012). https://doi.org/10.1007/s00441-012-1383-y

Download citation

Keywords

  • Bladder cell
  • CD phenotypes
  • Cell transcriptomes
  • Bladder cancer
  • Gene expression
  • Cancer-associated stromal cells