Hyaluronan Metabolism is Associated with DNA Repair Genes in Breast and Colorectal Cancer. Screening of Potential Progression Markers Using qPCR

Abstract

<jats:p>In this work, we compared mRNA levels of Hyaluronan (HA) metabolism members and BRCA genes, known to be involved in the tumoral process, between tumor and non-tumor adjacent tissue and its correlation with previously proposed biomarkers (ER, PR, HER2 and KI67) in order to assess their value as a progression biomarkers. We show alteration in HA metabolism in colorectal but not breast cancer. However, we found a decrease in Hyaluronidase 1 HYAL1 levels in the breast but not colorectal cancer. We also show lower HA levels in tumor compared with normal tissue that could indicate a possible influence of tumor on its surrounding “normal” tissue. In both breast and colorectal cancer, CD44 and BRCA2 showed a strong positive correlation. Besides, our results show first indicators that qPCR of the analyzed genes could be used as an easy and low cost procedure for the evaluation of molecular markers we propose here.</jats:p>

Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells

“…In agreement with previous findings in MDA-MB-231 cells with the reduced expression of the PG/GAG linker region biosynthetic enzyme ß4GALT7 [25], a reduced expression of Sdc-1 was associated with an upregulation of HAS2 in MCF-7 cells, while the expression of HA receptor, RHAMM, was downregulated. Notably, previous reports have shown that HA secretion is higher in MDA-MD-231 than MCF-7 and is in correlation with ER-negative status [37], but both cell lines express a similar level of mRNA HAS-2 and its gene expression is not associated with hormonal receptors' ER/PR status [38,39]. Therefore, our results acquire significant weight to demonstrate that Sdc-1 and HA metabolism are functionally related, whereas Sdc-1 depletion also affected the HA signaling pathway in MDA-MB-231 cells, however, in a differential manner.…”

Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells

“…We extended the study by evaluating patients with breast cancer, using samples obtained from patients in the Hospital of our region. In the present study, we analyzed the expression of UGDH mRNA in tumoral (TT) and normal adjacent tissue (NAT) samples obtained from four breast cancer patients previously characterized according to ER, PR, HER2 and Ki67 status in our laboratory [ 34 ]. In three patients who were defined as HER2−, we observed an increase in UGDH expression in TT compared to NAT.…”

“…Similar results were found when evaluating the expression of UGDH in breast cancer cell lines with different aggressive phenotypes and ER, PR and HER2 status. On the other hand, the patient that showed a decrease in UGDH levels showed also a decrease in HA expression and HAS2 levels [ 34 ]. Although further studies are required to understand the function of this enzyme in breast cancer patients and its relation with HA metabolism, these results confirm the data observed in vitro and in silico, and indicate that the mechanisms in which UGDH is involved could be altered during breast cancer progression and treatment.…”

“…The patients were all female (four patients) with mean age 61.50 ± 6.6 yr. Histopathologic diagnosis for all the breast cancer patients was invasive carcinoma of no special type (NST). TNM stages were determined by a pathologist and specific markers status such as prolactin receptor (PR), estrogen receptor (ER), HER2 and Ki67 were analyzed previously in our laboratory [ 34 ].…”