Bone morphogenetic proteins (BMPs) are multi-functional growth factors primarily isolated from bone according to their osteoinductive capacity and exert their function by BMP pathway including BMP receptors and BMP-related Smad molecules. BMP pathway triggers various processes such as cellular migration, proliferation and differentiation, which are involved in physiological as well as in pathological conditions. As members of TGFbeta family they are also included in processes of epithelial- mesenchymal transition which is important in cancer progression. The aim of this study was to investigate the alteration of BMP pathway in colorectal cancer samples of patients who underwent the CRC surgery. This study was approved by Ethical committee of Clinical Hospital Centre and Faculty of Medicine. All samples were obtained with informed consent. The expression of BMP pathway in different stage of colorectal cancer was characterised by imunohistochemistry and western blot using Smad1/5/8 and pSmad1/5/8 antibody. The clinicopathologic data such as age, gender, Dukes staging and differentiation grade are also analysed. Additionally, the correlation with establish marker of cell proliferation, Ki67 was examined. Our results showed that colorectal cancer occurred most frequently in men (75%) and in older people (more than 60 years; 85%). The most common site of primary carcinoma was sigmoid colon and rectum (75%). According to Dukes staging, 55% of examined cancers were DukesB and 45% DukesC. In both stages, we have found the expression of total and active form of Smad1/5/8 which is higher in DukesB stage of colorectal cancer samples. We also found the positive correlation between Ki67 and Smad1/5/8 expression. These results suggested that BMP pathway has also important role in the carcinogenesis and alterations of this pathway could contribute to the cancer progression. Therefore, it could be concern that determination of the BMP pathway activity could be additional prognostic marker of colorectal cancer.
Disclosure: The authors declared no competing interests. This work was supported by the University of Rijeka (grant number 13.06.1.3.46) and Ministry of Science, Education and Sports of the Republic of Croatia (grant number 062-0620226-0209).