Top

Published in:

Open Access 01-04-2011 | Original Paper

Differential Inductive Signaling of CD90⁺ Prostate Cancer-Associated Fibroblasts Compared to Normal Tissue Stromal Mesenchyme Cells

Authors: Laura E. Pascal, Junkui Ai, Ricardo Z. N. Vêncio, Eneida F. Vêncio, Yong Zhou, Laura S. Page, Lawrence D. True, Zhou Wang, Alvin Y. Liu

Published in: Cancer Microenvironment | Issue 1/2011

Abstract

Prostate carcinomas are surrounded by a layer of stromal fibroblastic cells that are characterized by increased expression of CD90. These CD90⁺ cancer-associated stromal fibroblastic cells differ in gene expression from their normal counterpart, CD49a⁺CD90^lo stromal smooth muscle cells; and were postulated to represent a less differentiated cell type with altered inductive properties. CD90⁺ stromal cells were isolated from tumor tissue specimens and co-cultured with the pluripotent embryonal carcinoma cell line NCCIT in order to elucidate the impact of tumor-associated stroma on stem cells, and the ‘cancer stem cell.’ Transcriptome analysis identified a notable decreased induction of smooth muscle and prostate stromal genes such as PENK, BMP2 and ChGn compared to previously determined NCCIT response to normal prostate stromal cell induction. CD90⁺ stromal cell secreted factors induced an increased expression of CD90 and differential induction of genes involved in extracellular matrix remodeling and the RECK pathway in NCCIT. These results suggest that, compared to normal tissue stromal cells, signaling from cancer-associated stromal cells has a markedly different effect on stem cells as represented by NCCIT. Given that stromal cells are important in directing organ-specific differentiation, stromal cells in tumors appear to be defective in this function, which may contribute to abnormal differentiation found in diseases such as cancer.

Available only for authorised users

Cunha GR, Ricke W, Thomson A, Marker PC, Risbridger G, Hayward SW, Wang YZ, Donjacour AA, Kurita T (2004) Hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development. J Steroid Biochem Mol Biol 92(4):221–236PubMedCrossRef

Tuxhorn JA, Ayala GE, Rowley DR (2001) Reactive stroma in prostate cancer progression. J Urol 166(6):2472–2483PubMedCrossRef

Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR (2002) Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 8(9):2912–2923PubMed

Rowley DR (1998) What might a stromal response mean to prostate cancer progression? Cancer Metastasis Rev 17(4):411–419PubMedCrossRef

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 5:17PubMedCrossRef

Richardson AM, Woodson K, Wang Y, Rodriguez-Canales J, Erickson HS, Tangrea MA, Novakovic K, Gonzalez S, Velasco A, Kawasaki ES, Emmert-Buck MR, Chuaqui RF, Player A (2007) Global expression analysis of prostate cancer-associated stroma and epithelia. Diagn Mol Pathol 16(4):189–197PubMedCrossRef

Pascal LE, Goo YA, Vencio RZ, Page LS, Chambers AA, Liebeskind ES, Takayama TK, True LD, Liu AY (2009) Gene expression down-regulation in cd90+ prostate tumor-associated stromal cells involves potential organ-specific genes. BMC Cancer 9:317PubMedCrossRef

Dakhova O, Ozen M, Creighton CJ, Li R, Ayala G, Rowley D, Ittmann M (2009) Global gene expression analysis of reactive stroma in prostate cancer. Clin Cancer Res 15(12):3979–3989PubMedCrossRef

Ernst T, Hergenhahn M, Kenzelmann M, Cohen CD, Bonrouhi M, Weninger A, Klaren R, Grone EF, Wiesel M, Gudemann C, Kuster J, Schott W, Staehler G, Kretzler M, Hollstein M, Grone HJ (2002) Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue. Am J Pathol 160(6):2169–2180PubMedCrossRef

10.

Zhao H, Peehl DM (2009) Tumor-promoting phenotype of cd90hi prostate cancer-associated fibroblasts. Prostate 69(9):991–1000PubMedCrossRef

11.

Sung SY, Chung LW (2002) Prostate tumor-stroma interaction: molecular mechanisms and opportunities for therapeutic targeting. Differentiation 70(9–10):506–521PubMedCrossRef

12.

True LD, Zhang H, Ye M, Huang CY, Nelson PS, von Haller PD, Tjoelker LW, Kim JS, Qian WJ, Smith RD, Ellis WJ, Liebeskind ES, Liu AY (2010) Cd90/thy1 is overexpressed in prostate cancer-associated fibroblasts and could serve as a cancer biomarker. Mod Pathol 2010 Oct; 23(10):1346–56

13.

Pascal LE, Vencio RZ, Goo YA, Page LS, Shadle CP, Liu AY (2009) Temporal expression profiling of the effects of secreted factors from prostate stromal cells on embryonal carcinoma stem cells. Prostate 69(12):1353–1365PubMedCrossRef

14.

Damjanov I, Horvat B, Gibas Z (1993) Retinoic acid-induced differentiation of the developmentally pluripotent human germ cell tumor-derived cell line, nccit. Lab Invest 68(2):220–232PubMed

15.

Vencio EF, Pascal LE, Page LS, Denyer G, Wang AJ, Ruohola-Baker H, Zhang S, Wang K, Galas DJ, Liu AY (2010) Embryonal carcinoma cell induction of mirna and mrna changes in co-cultured prostate stromal fibromuscular cells. J Clin Pathol doi:1002/jcp.22464

16.

Liu AY, Zhang H, Sorensen CM, Diamond DL (2005) Analysis of prostate cancer by proteomics using tissue specimens. J Urol 173(1):73–78PubMedCrossRef

17.

Liu AY, True LD, LaTray L, Nelson PS, Ellis WJ, Vessella RL, Lange PH, Hood L, van den Engh G (1997) Cell-cell interaction in prostate gene regulation and cytodifferentiation. Proc Natl Acad Sci USA 94(20):10705–10710PubMedCrossRef

18.

Kassen A, Sutkowski DM, Ahn H, Sensibar JA, Kozlowski JM, Lee C (1996) Stromal cells of the human prostate: initial isolation and characterization. Prostate 28(2):89–97PubMedCrossRef

19.

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(2):249–264PubMedCrossRef

20.

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 Bioinform 7:286CrossRef

21.

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 7:19PubMedCrossRef

22.

Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) David: database for annotation, visualization, and integrated discovery. Genome Biol 4(5):P3PubMedCrossRef

23.

Nielsen H, Engelbrecht J, Brunak S, von Heijne G (1997) A neural network method for identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Int J Neural Syst 8(5–6):581–599PubMedCrossRef

24.

Krogh A, Larsson B, von Heijne G, Sonnhammer EL (2001) Predicting transmembrane protein topology with a hidden markov model: application to complete genomes. J Mol Biol 305(3):567–580PubMedCrossRef

25.

Zhang H, Liu AY, Loriaux P, Wollscheid B, Zhou Y, Watts JD, Aebersold R (2007) Mass spectrometric detection of tissue proteins in plasma. Mol Cell Proteomics 6(1):64–71PubMed

26.

Clark JC, Thomas DM, Choong PF, Dass CR (2007) Reck—a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer. Cancer Metastasis Rev 26(3–4):675–683PubMedCrossRef

27.

Riddick AC, Shukla CJ, Pennington CJ, Bass R, Nuttall RK, Hogan A, Sethia KK, Ellis V, Collins AT, Maitland NJ, Ball RY, Edwards DR (2005) Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br J Cancer 92(12):2171–2180PubMedCrossRef

28.

Moses MA, Wiederschain D, Loughlin KR, Zurakowski D, Lamb CC, Freeman MR (1998) Increased incidence of matrix metalloproteinases in urine of cancer patients. Cancer Res 58(7):1395–1399PubMed

29.

Taranger CK, Noer A, Sorensen AL, Hakelien AM, Boquest AC, Collas P (2005) Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Mol Biol Cell 16(12):5719–5735PubMedCrossRef

30.

Pascal LE, Oudes AJ, Petersen TW, Goo YA, Walashek LS, True LD, Liu AY (2007) Molecular and cellular characterization of abcg2 in the prostate. BMC Urol 7:6PubMedCrossRef

Title: Differential Inductive Signaling of CD90+ Prostate Cancer-Associated Fibroblasts Compared to Normal Tissue Stromal Mesenchyme Cells
Authors: Laura E. Pascal
Junkui Ai
Ricardo Z. N. Vêncio
Eneida F. Vêncio
Yong Zhou
Laura S. Page
Lawrence D. True
Zhou Wang
Alvin Y. Liu
Publication date: 01-04-2011
Publisher: Springer Netherlands
Published in: Cancer Microenvironment / Issue 1/2011
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI: https://doi.org/10.1007/s12307-010-0061-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

Myeloid Cells in Cancer Progression: Unique Subtypes and Their Roles in Tumor Growth, Vascularity, and Host Immune Suppression

Microdialysis Combined with Proteomics for Protein Identification in Breast Tumor Microenvironment In Vivo

The Potential Role of MT and Vimentin Immunoreactivity in the Remodeling of the Microenvironment of Parotid Adenocarcinoma

The Involvement of RCAS1 in Creating a Suppressive Tumor Microenvironment in Patients with Salivary Gland Adenocarcinoma

Lumican Reduces Tumor Growth Via Induction of Fas-Mediated Endothelial Cell Apoptosis

Expression of Human MDGA1 Increases Cell Motility and Cell-Cell Adhesion and Reduces Adhesion to Extracellular Matrix Proteins in MDCK Cells

Keynote webinar | Spotlight on antibody–drug conjugates in cancer