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Journal of Cancer Research and Clinical Oncology

, Volume 143, Issue 2, pp 351–359 | Cite as

Stromal factors involved in human prostate cancer development, progression and castration resistance

  • Noemi Eiro
  • Jesus Fernandez-Gomez
  • Raquel Sacristán
  • Belen Fernandez-Garcia
  • Beatriz Lobo
  • Jorge Gonzalez-Suarez
  • Alejandro Quintas
  • Safwan Escaf
  • Francisco J. VizosoEmail author
Original Article – Clinical Oncology

Abstract

Purpose

To detect new predictive markers from the prostate cancer tissue, to study the expression by cultured cancer-associated fibroblasts (CAFs) of stromal factors implicated in prostate carcinogenesis, and to compare their expressions in localized, metastatic, castration-sensitive (CSCP), castration-resistant prostate tumors (CRCP) as well as in fibroblasts from benign prostatic hyperplasia (BPH).

Materials and methods

The genomic expression of 20 stroma-derived factors, including the androgen receptor (AR), growth factors (FGF2, FGF7, FGF10, HGF, TGFβ, PDGFB), protein implicated in invasion (MMP-2, MMP-9 and MMP-11), inflammation (IL-6, IL-17, STAT-3 and NFκB), stroma/epithelium interaction (CDH11, FAP, CXCL12 and CXCL14) and chaperones (HPA1A and HSF1), was evaluated in cultured fibroblasts both from BHP and prostate carcinomas (PCa). After isolation and culture of fibroblasts by biopsy specimens, RNA was isolated and genomic studies performed.

Results

Finally, 5 BPH and 37 PCa specimens were selected: clinically localized (19), metastatic (5), CSCP (7) and CRPC (6). Interleukin-17 receptor (IL-17RB) was highly expressed in CAFs compared with fibroblasts from BPH. However, metalloproteinase-2 and chemokine ligand 14 (CXCL14) were expressed at higher levels by fibroblasts from BPH. The fibroblastic growth factor-7 was highly expressed by CAFs from localized tumors, but metalloproteinase-11 in metastatic tumors. MMP-11, androgen receptor (AR) and heat–shock-70kda-protein-1A (HSPA1A) expressions were significantly higher in CAFs from CRPC.

Conclusions

These results demonstrate a CAFs heterogeneity among prostate carcinomas with regard to some molecular profile expressions that may be relevant in tumor development (IL-17RB), progression (MMP-11) and castration resistance (AR, MMP-11 and HSPA1A).

Keywords

Cancer-associated fibroblasts (CAFs) Tumor stroma Metastatic cancer Castration-resistant prostate cancer Androgen deprivation therapy 

Notes

Acknowledgements

This work was supported by a grant from Abbvie Inc, Chicago (Study No: ACA-SPAI-10-24). The expert technical assistance of Sandra Cid was gratefully acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Noemi Eiro
    • 1
  • Jesus Fernandez-Gomez
    • 2
  • Raquel Sacristán
    • 3
  • Belen Fernandez-Garcia
    • 1
  • Beatriz Lobo
    • 2
  • Jorge Gonzalez-Suarez
    • 2
  • Alejandro Quintas
    • 2
  • Safwan Escaf
    • 1
  • Francisco J. Vizoso
    • 1
    Email author
  1. 1.Unidad de InvestigaciónFundación Hospital de JoveGijónSpain
  2. 2.Unidad de Urología, Hospital Central de AsturiasUniversidad de OviedoOviedoSpain
  3. 3.Servicio de UrologíaFundación Hospital de JoveGijónSpain

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