Osteonectin (SPARC) prognostic value in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is common malignancy among men worldwide. To date only few molecular markers are available to predict its course and outcome. SPARC is considered to be promising prognostic marker of PCa due to its involvement in various cancer processes. MATERIALS AND METHODS: study was conducted on PCa surgical primary tumor samples, obtained from 84 patients. Level of SPARC mRNA expression was estimated using RT-qPCR. To identify SPARC protein (osteonectin) in prostate tissue, immunohistochemical analysis was conducted. Bioinformatical analysis was performed on UALCAN and TNMplot resources. RESULTS: bioinformatical analysis demonstrated that SPARC mRNA levels are decreased in PCa samples, in comparison to normal tissue. In patients with lymph node metastases its levels are 1.26 times higher; p = 4.66E-02, than in N0 category. Ex vivo study demonstrated that SPARC expression was elevated on both mRNA and protein levels in PCa patients with lymph node metastases (by 2.34 and 1.91, respectively, p < 0.05). We established higher levels of SPARC mRNA and protein in PCa patients with T3 tumors, as well as high Gleason score. Estimation of survival rates demonstrated that PCa patients with a high level of SPARC mRNA and protein have decreased overall 2-year survival. CONCLUSIONS: SPARC protein was overexpressed on mRNA and protein levels in patients with presence of lymph node metastases and higher Gleason score of tumors. Also, both mRNA and protein upregulation were associated with worse survival rates. The current study has therefore provided further evidence that SPARC is indeed linked to the prognosis and aggressiveness of human PCa.

Does insulin make breast cancer cells resistant to doxorubicin toxicity?

The effects of insulin on the doxorubicin (Dox) sensitivity of breast cancer cell line MCF-7 and its Dox-resistant counterpart MCF-7/Dox were studied and glucose metabolism, content of essential minerals, and the expression of several microRNAs in these cells upon exposure to insulin and Dox were compared. Cell viability colorimetric assay, colorimetric enzymatic technique, flow cytometry, immunocytochemical techniques, inductively-coupled plasma atomic emission spectroscopy, and quantitative polymerase chain reaction were used in the study. We found that insulin in high concentration significantly suppressed Dox toxicity, especially in parental MCF-7 cell line. The increase in proliferative activity triggered by insulin in MCF-7 but not MCF-7/Dox cells occurred in the setting of the increased level of specific binding sites for insulin and increased glucose uptake. Insulin treatment of MCF-7 cells in low and high concentrations resulted in the increase of Mg, Ca, and Zn content while in DOX-resistant cells, only Mg content increased upon exposure to insulin. High concentration of insulin increased the expression of kinase Akt1, P-glycoprotein 1 (P-gp1) and DNA excision repair protein ERCC-1 in MCF-7 cells, while in MCF-7/Dox cells, Akt1 expression decreased, and cytoplasmic expression of P-gp1 increased. In addition, insulin treatment affected expression of miR-122-5p, miR-133a-3p, miR-200b-3p, and miR-320a-3p. The decreased manifestation of biological effects of insulin in Dox-resistant cells could be partly explained by the different patterns of energy metabolism in MCF-7 cells and their Dox-resistant counterpart.

Mast cells as a tumor microenvironment factor associated with the aggressiveness of prostate cancer.

We aimed to investigate the relationship between the degree of mast cells' (MCs) infiltration and clinicopathological features of prostate cancer (PCa) malignancy and to find out the possible mechanisms of the involvement of these cells in the formation of the aggressive course of the PCa development. The study was conducted on the clinical material of 60 patients with PCa of stages II-III. MCs in the PCa tissue were determined by a histochemical method using toluidine blue. The expression of osteopontin (OPN) was studied by the immunohistochemical method. The expression of miRNA-21, -126, -146a, -181a, and -221 was investigated by quantitative real-time PCR. Statistical processing of the results was performed using the GraphPad Prism 8 program. Our results demonstrated that the increased level of infiltration and degranulation of MCs in the PCa tissue was associated with such indices of the malignancy of the tumor process as the Gleason score and the preoperative PSA level in the blood serum of patients. A high level of MCs infiltration of the PCa tissue was associated with a significant decrease in the two-year recurrence-free survival rates of the patients by 23.3% (р=0.0455). A high degree of MCs infiltration of the PCa tissue was associated with 1.2 times (p=0.0347) higher level of OPN expression and 1.7 (p=0.0051) and 1.65 (p=0.0087) times lower levels of miR-126 and miR-181a expression, respectively. The obtained results indicate the participation of MCs as a factor of the tumor microenvironment in the PCa progression.