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Prostate Cancer: Stroma Implication in Progression, Diagnosis and Prognosis
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Prostate Cancer: Stroma Implication in Progression, Diagnosis and Prognosis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 5395

Special Issue Editor

Dr. Noemi Eiro Diaz

E-Mail Website
Guest Editor
Research Unit, Hospital Fundación de Jove, Avda. Eduardo de Castro 161, 33290 Gijón, Spain
Interests: mesenchymal stem cells; conditioned medium; secretome; breast cancer; prostate cancer; metalloproteinases; stroma, fibroblasts; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate cancer is one of the most common forms of cancer in men and one of the leading causes of cancer death worldwide. The prostatic gland is composed of two main compartments: epithelial and stromal, and their interaction is necessary for prostate development and differentiation. Similarly, prostate cancer is composed of both malignant epithelial cells and reactive stroma, which contributes to the growth, development, and progression of the tumor. 

The tumor stroma is composed of fibroblasts, immune cells, myofibroblasts and endothelial cells; the two first cell types being predominant. The factors expressed by the stroma act on the prostate gland and have been related to an increased risk of malignancy. Indeed, the interplay between the epithelial and stromal cells that both interact under the influence of androgen, cytokines and growth factors is among the most important, resulting in a formation of microenvironment appropriate for cancer growth and development.

A better understanding of the role of the stroma in the development and progression of prostate cancer constitutes a necessary process to achieve a correct stratification of the risk of this pathology among men with localized disease and the revelation of possible therapeutic targets.

Dr. Noemí Eiró
Guest Editor

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Published Papers (2 papers)

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14 pages, 1248 KiB  
Article
Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer
by Valentina Doldi, Mara Lecchi, Silva Ljevar, Maurizio Colecchia, Elisa Campi, Giovanni Centonze, Cristina Marenghi, Tiziana Rancati, Rosalba Miceli, Paolo Verderio, Riccardo Valdagni, Paolo Gandellini and Nadia Zaffaroni
Int. J. Mol. Sci. 2022, 23(14), 7987; https://doi.org/10.3390/ijms23147987 - 20 Jul 2022
Cited by 5 | Viewed by 2037
Abstract
Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease [...] Read more.
Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients. Full article
(This article belongs to the Special Issue Prostate Cancer: Stroma Implication in Progression, Diagnosis and Prognosis)
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20 pages, 4443 KiB  
Article
Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases
by Cinzia Antognelli, Lorella Marinucci, Roberta Frosini, Lara Macchioni and Vincenzo Nicola Talesa
Int. J. Mol. Sci. 2021, 22(19), 10191; https://doi.org/10.3390/ijms221910191 - 22 Sep 2021
Cited by 12 | Viewed by 2520
Abstract
Bone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boosting [...] Read more.
Bone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boosting research to identify additional mechanisms that may be involved in this two-directional talk. Here, we investigated whether and how 5-hydro-5-methylimidazolone (MG-H1), a specific methylglyoxal (MG)-derived advanced glycation end product (AGE), was a novel player in the dialogue between PCa and OB to drive PCa bone metastases. Conditioned medium from osteotropic PC3 PCa cells, pre-treated or not with a specific MG scavenger, was administrated to human primary OB and cell morphology, mesenchymal trans-differentiation, pro-osteogenic determinants, PCa-specific molecules, and migration/invasion were studied by phase-contrast microscopy, real-time PCR, western blot and specific assays, respectively. We found that PC3 cells were able to release MG-H1 that, by binding to the receptor for AGEs (RAGE) on OB, reprogrammed them into a less-differentiate phenotype, endowed with some PCa-specific molecular features and malignant properties, in a mechanism involving reactive oxidative species (ROS) production and NF-kB pathway activation. These findings provide novel insights into the mechanisms of PCa osteoblastic metastases and foster in vivo research toward new therapeutic strategies interfering with PCa/OB cross-talk. Full article
(This article belongs to the Special Issue Prostate Cancer: Stroma Implication in Progression, Diagnosis and Prognosis)
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