Gene Expression Profile of Stromal Factors in Cancer-Associated Fibroblasts from Prostate Cancer

Recent investigations point at the stromal microenvironment to assess additional diagnostic information and provide new therapeutic targets in cancer. The aim of the study was to contribute to the characterization of the phenotype of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa) comp...

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Bibliographic Details
Published in:Diagnostics (Basel) 2022-06, Vol.12 (7), p.1605
Main Authors: Eiro, Noemi, Fernández-Gómez, Jesús María, Gonzalez-Ruiz de León, Cristina, Fraile, Maria, Gonzalez-Suarez, Jorge, Lobo-Rodríguez, Beatriz, García-Rodríguez, Jorge, Escaf, Safwan, Vizoso, Francisco J
Format: Article
Language:English
Subjects:
Age
androgen deprivation therapy
Androgens
Angiogenesis
Biopsy
Cancer
cancer-associated fibroblasts CAFs
Connective tissue cells
Extracellular matrix
Fibroblasts
Gene expression
Genetic aspects
Growth factors
Lymphatic system
Medical prognosis
Metastasis
metastatic cancer
MMP11
Oncology, Experimental
Prostate cancer
Risk factors
Scintigraphy
tumor stroma
Tumors
Ultrasonic imaging
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Summary:Recent investigations point at the stromal microenvironment to assess additional diagnostic information and provide new therapeutic targets in cancer. The aim of the study was to contribute to the characterization of the phenotype of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa) compared with normal prostate-associated fibroblasts (NAFs) and fibroblasts from benign prostatic hyperplasia (BPH). Three patient populations were prospectively recruited: 23 patients with new localized PCa, 14 patients with advanced PCa treated with androgenic deprivation therapy (ADT), and 7 patients with BPH. Gene expression of 20 stroma-derived factors, including the androgen receptor (AR), chaperones (HSPA1A and HSF1), growth factors (FGF2, FGF7, FGF10, HGF, PDGFB, and TGFβ), proteins implicated in invasion (MMP2, MMP9, and MMP11), inflammation (IL6, IL17RB, NFκB, and STAT3), and in-stroma/epithelium interaction (CDH11, CXCL12, CXCL14, and FAP), was evaluated. Localized PCa CAFs showed a significant higher expression of FGF7, IL6, MMP2, and MMP11 compared with NAFs or IL17RB compared with BPH fibroblasts, but significantly lower expression of FGF10 and IL17RB compared with NAFs or CXCL14 compared with BPH fibroblasts. In addition, CAFs from ADT-resistant PCa showed significantly higher MMP11 and NFκB but significant lower TGFβ expression compared with CAFs from ADT-sensitive tumors. Our results contribute to defining the CAFs phenotypes associated to PCa progression, which may contribute to the diagnosis and design of alternative therapies in PCa.
ISSN:2075-4418
2075-4418
DOI:10.3390/diagnostics12071605