keratan-sulfate and Colorectal-Neoplasms

Lumican is a member of a small leucine-rich proteoglycan family, and it is reportedly overexpressed in human breast cancer. The expression of lumican in the extracellular matrix in breast cancer is associated with a high tumor grade, low estrogen receptor levels and young age. Lumican expression has been previously reported in colorectal cancer, but the role of lumican in the tumor is not well understood. In this study, we examined the expression and role of lumican in advanced colorectal cancer. Immunohistochemical staining was performed on 158 patients who underwent curative surgery for advanced colorectal cancer with lymph node metastasis. In the normal colorectal tissues, lumican immunoreactivity was observed in the fibroblasts and neural cells, but not in the colorectal epithelial cells. Lumican was localized in the cytoplasm of the cancer cells and its overexpression was detected in 99 of the 158 (62.7%) colorectal cancer patients. Clinicopathologically, there was no association of lumican expression with age, sex, histological typing, or venous and lymphatic invasion. However, lumican expression tended to correlate with the spread of lymph node metastasis and the depth of tumor invasion (p=0.136 and 0.135, respectively). Furthermore, the survival rate was significantly lower in patients with a high lumican expression level than in those with a low lumican expression level (p=0.048). These results indicate that lumican expression is a potential prognostic factor in patients with advanced colorectal cancer with nodal metastasis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chondroitin Sulfate Proteoglycans; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratan Sulfate; Lumican; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Survival Analysis; Survival Rate

Lumican is a member of a small leucine-rich proteoglycan family and its overexpression in human breast cancer tissues is reported to influence the growth of cancer cells. In the present study, we aimed to clarify the expression of lumican mRNA and its protein in human colorectal cancer cell lines and their localization in normal and cancerous colorectal tissues. Reverse transcription-polymerase chain reaction and western blot analysis revealed lumican mRNA and its protein expression in COLO 205, DLD-1, HCT-15, SW 480 and WiDr colorectal cancer cell lines. The lumican in colorectal cancer cells had non-sulfated or poorly sulfated polylactosamine side chains. Based on its immunoreactivity, the lumican protein was found to be localized in fibroblasts and stromal tissues of normal colorectal tissues, but not in colorectal epithelial cells. In colorectal cancer tissues, the lumican was strongly localized in cancer cells in eight of 12 cancer cases. The lumican protein was also localized in epithelial cells with mild reactive dysplasia and fibroblasts adjacent to cancer cells. Lumican mRNA was expressed in cancer cells and adjacent fibroblasts, and epithelial cells. These findings may indicate that the lumican protein synthesized by cancer cells, fibroblasts and epithelial cells with mild reactive dysplasia found adjacent to cancer cells may affect the growth of human colorectal cancer cells.

Topics: Blotting, Western; Chondroitin Sulfate Proteoglycans; Colorectal Neoplasms; Epithelial Cells; Fibroblasts; Humans; Immunohistochemistry; In Situ Hybridization; Keratan Sulfate; Lumican; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured