Stromal-epithelial interactions in early neoplasia

Issue title: Translational Pathology of Early Cancer

Guest editors: Sudhir Srivastavax and William E. Grizzley

Article type: Research Article

Authors: Liu, Alvin Y.^{a; *} | Pascal, Laura E.^{a; c} | Vêncio, Ricardo Z.^b | Vêncio, Eneida F.^{b; d}

Affiliations: [a] Department of Urology and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA | [b] Genetics Department, University of São Paulo's Medical School at Ribeirão Preto, Brazil | [c] University of Pittsburgh Medical Center, Department of Urology, Pittsburgh, PA, USA | [d] Universidade Federal de Goiás, Faculdade de Odontologia, Departamento de Patologia, Praça Universitária, s/n, 74605-220, Goiania, GO, Brazil | [x] Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA | [y] Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: [*] Corresponding author: Alvin Y. Liu, University of Washington, Department of Urology, USA. Tel: +1 206 221 0603; E-mail: [email protected].

Abstract: In prostate tumors, both the epithelial and stromal mesenchyme compartments show gene expression changes from their respective normal counterpart. In fact, there are more such changes in the stroma than the epithelium. These include down-regulated expression of genes involved in smooth muscle cell differentiation and those differentially expressed between prostate and bladder, i.e., organ-restricted. In development, the stromal cell type mediates tissue formation from differentiation of stem or progenitor cells. Diseases like cancer may arise as a result of defective stromal signaling. Stromal signaling can be demonstrated by co-culture of stromal cells and embryonal carcinoma NCCIT cells used as a stem cell substitute. In co-culture, stromal cells induce NCCIT cells through diffusible molecules to lose stem cell gene expression, gain expression of prostate genes, alter cytomorphology, and lower proliferation. This NCCIT response is varied as co-cultured bladder stromal cells induce a different gene expression. At the same time, NCCIT factors also affect gene expression of co-cultured stromal cells. NCCIT induces normal prostate tissue (NP) stromal cells to become more like cancer-associated (CP) stromal cells in both mRNA and microRNA expression. In contrast, NCCIT shows minimal effect on CP stromal cells. CP stromal cells may represent a less differentiated state in the prostate stromal cell lineage.

Keywords: Prostate cancer, cell type transcriptomes, CD26⁺ cancer cells, CD90⁺ cancer-associated stromal cells, Gleason patterns, stromal induction of stem cells, NCCIT embryonal carcinoma cells, in vitro co-culture, cell-cell interaction, intercellular signaling molecules, mRNA and miRNA expression changes

DOI: 10.3233/CBM-2011-0174

Journal: Cancer Biomarkers, vol. 9, no. 1-6, pp. 141-155, 2011