Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples.

Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.

Antioxidant enzymes change in different non-metastatic stages in tumoral and peritumoral tissues of colorectal cancer.

Antioxidant defences and oxidative stress are related to development, progression and malignancy of colorectal cancer. However, their role in early stages of cancer remains unknown. More and more recent studies have revealed that non-tumour adjacent tissue is not a normal tissue. Thus, our aim was to analyse protein levels of MnSOD (Manganese Superoxide Dismutase), acMnSOD (Acetylated Manganese superoxide Dismutase), SIRT3 (Sirtuin 3), CuZnSOD (Cupper Zinc Superoxide Dismutase), CAT (Catalase), GPx (Glutathione Peroxidase), and GRd (Glutathione Reductase) both in tumour and non-tumour adjacent tissue from colorectal cancer patients by western blot. Non-tumour adjacent tissue seemed to have higher levels of antioxidant enzymes that detoxify hydrogen peroxide compared to tumour tissue. In contrast, tumour tissue had higher levels of MnSOD and acMnSOD. Furthermore, most of the proteins analysed showed significant differences between stage I and II in both non-tumour adjacent and tumour tissue. This could indicate that antioxidant enzymes, especially MnSOD, play a crucial role in early stages of colorectal cancer in both tissues, so they could be analysed as novel biomarkers to improve colorectal cancer diagnosis.

Estrogen down-regulates uncoupling proteins and increases oxidative stress in breast cancer.

Oxidative stress has been postulated as one of the mechanisms underlying the estrogen carcinogenic effect in breast cancer. Estrogens are known to increase mitochondrial-derived reactive oxygen species (ROS) by an unknown mechanism. Given that uncoupling proteins (UCPs) are key regulators of mitochondrial energy efficiency and ROS production, our aim was to check the presence and activity of UCPs in estrogen receptor (ER)-positive and ER-negative breast cancer cells and tumors, as well as their relation to oxidative stress. Estrogen (1 nM) induced higher oxidative stress in the ER-positive MCF-7 cell line, showing increased mitochondrial membrane potential, H(2)O(2) levels, and DNA and protein damage compared to ER-negative MDA-MB-231 cells. All isoforms of uncoupling proteins were highly expressed in ER-positive breast cancer cells and tumors compared to negative ones. ROS production in mitochondria isolated from MCF-7 was increased by inhibition of UCPs with GDP, but not in mitochondria from MDA-MB-231. Estrogen treatment decreased uncoupling protein and catalase levels in MCF-7 and decreased GDP-dependent ROS production in isolated mitochondria. On the whole, these results suggest that estrogens, through an ER-dependent mechanism, may increase mitochondrial ROS production by repressing uncoupling proteins, which offers a new perspective on the understanding of why estrogens are a risk factor for breast cancer.