engleski

BMP signaling pathway in colorectal cancer

Colorectal cancer is common cancer of the digestive tract with increasing incidence in the last decade. The higher incidence was observed in developed countries and connection with typical Western lifestyle and diet was emphasized. Colorectal cancer is the third most common cancer and is the second leading cause of death because of cancer. Extensive research was conducted to explore the genes and factors that may trigger the initiation and the progression of colorectal cancer (1). Among the genes which are known that affect the cancer development, BMPs and their signaling pathway have been under intensive research (2, 3). BMP signaling is required for the maintenance of intestinal epithelia stem cell, maturation of secretory cell lineage and apoptosis of mature colonic epithelial cells (4). Previously, we have shown the expression profile of BMPs and BMP pathway components in experimentally induced colitis (5). BMP pathway is preserved in the colon of diseased animals and its expression during experimentally colitis is recovered by the BMP7 therapy. To further characterize the role of BMPs in the intestine pathophysiology, we have studied the alteration of BMP signaling pathway in colon cancer samples of patients who underwent CRC surgery. The normal colon tissues samples were used as control. The patient and tumor characteristics such as age, gender, tumor location, Duke’s stage and grade differentiation are analyzed. The BMP signaling pathway expression was investigated using immunohistochemistry and Western blott. Also, we explored the expression of Ki-67, a typical marker of cell proliferation and the presence of neutrophils. Our results showed that adenocarcinoma represent the most common pathology and the sigmoid colon and rectum are the most common sites of primary carcinoma localization (75%). According to gender and age, colon cancer occurred more frequently in men (75%) and in the elderly (more than 60 years ; 80%). Smad1/5/8 cytoplasmatic and pSmad1/5/8 nuclear staining was present in all colon cancer samples and difference was found in intensity of staining which is also confirmed by Western blot. The nuclear staining of Ki-67 was observed in all colon cancer samples with the common presence of 50% of positive cells. The neutrophils are present in 50% of colon cancer samples. They are found at the border between the tumor cells and surrounding normal tissue and in areas of tumor necrosis. These results suggested that the BMP pathway is preserved and active in colon cancer but alteration of this pathway is occurred in the different stages of colon cancer.

bone morphogenetic proteins. colorectal cancer; BMP pathway

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