scholarly journals The relationship of obesity and prostate cancer (review)

2020 ◽  
Vol 17 (2) ◽  
pp. 147-155
Author(s):  
Maxim N. Peshkov ◽  
Galina P. Peshkova ◽  
Igor V. Reshetov

Obesity is a critical risk factor for prostate cancer (PCa). Adipose tissue plays an important role in tumor development, including growth, invasion, and metastasis. Diet and dietary components affect the progression of prostate cancer; however, the mechanisms underlying these associations remain unclear. Extraprostatic prostate tumor cells form a new microenvironment in the periprostatic adipose tissue, which alters these interactions and promotes tumor progression. Hyperinsulinemia leads to an increase in the level of free or biologically active insulin-like growth factor (IGF-1) due to a decrease in the production of IGF-binding proteins. Hypoandrogenism promotes the development of a more aggressive type of prostate cancer (higher Gleason scores). Adipokines of adipose tissue and cytokines (for example, interleukin-6 (IL-6) and tumor necrosis factor (TNF-), angiogenic factors (for example, vascular endothelial growth factor (VEGF), apelin (AGTRL1) and other factors (for example, leptin and adiponectin) have multiple effects on prostate cancer cells. Tumor cells interact directly or indirectly with adipocytes. Yellow (inactive) bone marrow is adipose tissue with separate islands of reticular tissue. It is located in the medullary canals of the tubular bones and in parts of the cells of the cancellous bone. Bone tissue is the object of the most frequent metastasis in prostate cancer, and with age, the content of fat cells in it increases. Bone marrow adipose tissue interacts with tumor cells, osteoblasts and other stromal cells and participates in the organization of the tumor microenvironment. Adipokines are key molecules in the interaction between tumor cells and adipose tissue, which is carried out through various mechanisms. A better understanding of the role of adipose tissue in the induction and progression of prostate cancer will lead to effective therapeutic strategies for this disease.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
C. Panabières ◽  
J. Vendrell ◽  
O. Pellé ◽  
X. Rebillard ◽  
S. Riethdorf ◽  
...  

1001 Background: Metastasis is the main cause of cancer-related death. Single disseminated tumor cells (DTC) can be detected by sensitive immunocytochemical and molecular technologies, but it is still unclear whether these cells are viable and biologically active. Methods: We applied a novel enzyme-linked immunospot assay (‘EPISPOT‘) that reveals a fingerprint of specific proteins secreted from single viable epithelial tumor cells. The membrane of ELISPOT plates were coated with monoclonal antibodies against the tumor-associated marker proteins mucin-1 (MUC1) for breast cancer and prostate-specific antigen (PSA) for prostate cancer. In addition, dual fluorescent EPISPOT assays were developed to characterize MUC1+ and PSA+ cells (i.e. CK19, FGF2 secretion). Results: Even in the absence of overt metastases (stage M0), the EPISPOT assay revealed viable tumor cells in the peripheral blood of 65% of prostate cancer patients (n=31) and the bone marrow of 54% of breast cancer patients (n=37). Respective samples from non-carcinoma controls were EPISPOT- negative, whereas 80 to 100% of samples from metastatic patients (stage M1, n=40) were positive. The number of EPISPOT-positive cells in M0-patients ranged from 2 to 197 in the blood of prostate cancer patients and 1 to 262 in the bone marrow of breast cancer patients, while M1- patients showed significantly higher counts (prostate cancer, 1–684; breast cancer, 4–813). Interestingly, subsets of MUC1- or PSA-secreting cells expressed a breast stem cell-like phenotype (MUC1-/CK19+) or secreted FGF-2 as factor relevant for the growth of DTC, respectively. Conclusions: A significant fraction of cancer patients harbor viable and biologically active tumor cells in their blood and bone marrow, even in the absence of overt metastases. The multiparameter EPISPOT assay helps to identify these putative metastatic precursor cells. No significant financial relationships to disclose.


2021 ◽  
Vol 22 (11) ◽  
pp. 5560
Author(s):  
Alejandro Álvarez-Artime ◽  
Belén García-Soler ◽  
Rosa María Sainz ◽  
Juan Carlos Mayo

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.


2009 ◽  
Vol 27 (10) ◽  
pp. 1549-1556 ◽  
Author(s):  
Dorothea Weckermann ◽  
Bernhard Polzer ◽  
Thomas Ragg ◽  
Andreas Blana ◽  
Günter Schlimok ◽  
...  

Purpose The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease. Patients and Methods Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization. Results Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis. Conclusion Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.


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