Conversion of Prostate Adenocarcinoma to Small Cell Carcinoma-Like by Reprogramming.

The lineage relationship between prostate adenocarcinoma and small cell carcinoma was studied by using the LuCaP family of xenografts established from primary neoplasm to metastasis. Expression of four stem cell transcription factor (TF) genes, LIN28A, NANOG, POU5F1, SOX2, were analyzed in the LuCaP lines.

These genes, when force expressed in differentiated cells, can reprogram the recipients into stem-like induced pluripotent stem (iPS) cells. Most LuCaP lines expressed POU5F1, while LuCaP 145. 1, representative of small cell carcinoma, expressed all four. Through transcriptome database query, many small cell carcinoma genes were also found in stem cells. To test the hypothesis that prostate cancer progression from "differentiated" adenocarcinoma to "undifferentiated" small cell carcinoma could involve re-expression of stem cell genes, the four TF genes were transfected via lentiviral vectors into five adenocarcinoma LuCaP lines - 70CR, 73CR, 86. 2, 92, 105CR - as done in iPS cell reprogramming. The resultant cells from these five transfections displayed a morphology of small size and dark appearing unlike the parentals. Transcriptome analysis of LuCaP 70CR* (* to denote transfected progeny) revealed a unique gene expression close to that of LuCaP 145. 1. In a prostate principal components analysis space based on cell-type transcriptomes, the different LuCaP transcriptome datapoints were aligned to suggest a possible ordered sequence of expression changes from the differentiated luminal-like adenocarcinoma cell types to the less differentiated, more stem-like small cell carcinoma types and LuCaP 70CR*. Prostate cancer progression can thus be molecularly characterized by loss of differentiation with re-expression of stem cell genes. This article is protected by copyright. All rights reserved.

Journal of cellular physiology. 2016 Jan 15 [Epub ahead of print]

Gisely T Borges, Eneida F Vêncio, Sue-Ing Quek, Adeline Chen, Diego M Salvanha, Ricardo Z N Vêncio, Holly M Nguyen, Robert L Vessella, Christopher Cavanaugh, Carol B Ware, Pamela Troisch, Alvin Y Liu

Department of Urology, University of Washington, Seattle, Washington. , Department of Urology, University of Washington, Seattle, Washington. , Department of Urology, University of Washington, Seattle, Washington. , Department of Urology, University of Washington, Seattle, Washington. , Department of Computing and Mathematics, FFCLRP, University of São Paulo, Brazil. , Department of Computing and Mathematics, FFCLRP, University of São Paulo, Brazil. , Department of Urology, University of Washington, Seattle, Washington. , Department of Urology, University of Washington, Seattle, Washington. , Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington. , Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington. , Institute for Systems Biology, Seattle, Washington. , Department of Urology, University of Washington, Seattle, Washington.

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