Prostate field cancerization and exosomes: Association between CD9, early growth response 1 and fatty acid synthase

Abstract

Intracapsular and well-defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre-malignancy. Such alterations in histologically normal tumor-adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FASN). However, the molecular etiology of prostate field cancerization, including EGR-1 and FASN upregulation, remains largely unknown. It was thus hypothesized that extracellular vesicles, notably exosomes, released by tumor lesions may induce molecular alterations in the surrounding tissues, resulting in field cancerization, priming the tissue, and ultimately promoting multifocal tumorigenesis, which is often observed in prostate cancer. Towards testing this hypothesis, the current study, to the best of our knowledge, for the first time, presents correlative protein expression data, generated in disease-free, tumor-adjacent and cancerous human prostate tissues by quantitative immunofluorescence, between the exosomal marker CD9, and EGR-1 and FASN. Despite the pilot character of the present study, and the static nature and heterogeneity of human tissues, the data suggest that CD9 expression itself is part of a field effect. In support of this hypothesis, the results suggest a possible contribution of exosomes to the induction of field cancerization in the prostate, particularly for EGR-1. These findings were corroborated in established cell models of cancerous (LNCaP) and non-cancerous (RWPE-1) human prostate epithelial cells. The findings of this study warrant further investigation into the functional interface between exosomes and field cancerization, as a detailed understanding of this characterization may lead to the development of clinical applications related to diagnosis and/or prognosis and targeted intervention to prevent progression from pre-malignancy to cancer.

Endometrial Cancer-Adjacent Tissues Express Higher Levels of Cancer-Promoting Genes than the Matched Tumors

“…A study by Chatterjee et al in breast cancer showed that fibroblasts isolated from tumor-adjacent tissue were tumor-activated and suppressed the clonogenic activity of normal breast epithelial progenitor cells while promoting the growth of malignant human mammary cells [ 80 ]. Recently, Amirrad et al suggested a possible contribution of tumor-derived exosomes to the upregulation of EGR-1 and FASN in tumor-adjacent prostatic tissues [ 81 ]. The important role of extracellular vesicles in dictating the phenotypes of tumor-surrounding cells through such a paracrine (secretory) influence has recently been demonstrated in other studies [ 53 ].…”

Field cancerization in breast cancer

“…The risk of breast cancer recurrence is determined primarily by histopathological evaluations of the tumor, the results of which are used to guide the therapeutic management of patients. However, genetic, epigenetic, and transcriptomic alterations have been identified in cancer-adjacent tissues of many epithelial cancers, including head and neck [7,12], colorectal [13,[42][43][44], skin [45,46], bladder [13,[47][48][49], lung [14,50], prostate [8,13,51,52], ovarian [53,54], and breast [10,[13][14][15][18][19][20][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. Moreover, persistent exposure to environmental risk factors (e.g.…”

Magnetofluoro-Immunosensing Platform Based on Binary Nanoparticle-Decorated Graphene for Detection of Cancer Cell-Derived Exosomes

“…FL was measured based on the LF-exo concentration. Actually, it was found that CD9 on an exosome could promote PC cell growth, indicating that CD9 could be a key exosome biomarker [ 29 , 30 ]. Therefore, in our study, AF488-CD9 functioned as a signal inducer to detect LF-exos.…”