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Published on: July 28, 2010
Loss of KAI1 expression in the progression of colorectal cancer
D P Lombardi1, J Geradts, J F Foley
1Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Abstract:
The transmembrane 4 superfamily member KAI1 (CD82) has been shown to inhibit pulmonary metastases in experimental metastasis models of prostate cancer and melanoma. KAI1 expression is decreased in the progression of common solid epithelial tumors of adulthood, including lung, prostate, breast, esophageal, gastric, pancreatic, and bladder cancers. The purpose of our study was to investigate KAI1 expression in the progression of human colorectal cancer. We first analyzed 20 colorectal cancer cell lines by immunoblot techniques. KAI1 was expressed heterogeneously, with the tumor cell lines having a more complex degree of glycosylation compared with that of the normal colonic tissue. KAI1 was highly expressed in the primary SW480 colon cancer cell line but was down-regulated 15-fold in the matched metastatic SW620 cell line. We also investigated KAI1 protein expression by immunohistochemistry in tissues from 84 patients with colorectal cancer. Each tissue section was assigned a KAI1 mean score (KMS) from 0 to 300 based on the product of the percentage of cells that stained for KAI1 and the intensity of the stain (1, 2, or 3). In 84 patients with colorectal cancer, KAI1 was expressed at high levels in normal colonic mucosa (KMS 226) but was expressed at lower levels in the primary tumors (KMS 65; P < 0.0001). In a subset of 12 patients with stage IV metastatic disease, we observed a progressive down-regulation of KAI1, from the normal adjacent colonic mucosa (KMS 193) to the primary tumor (KMS 72; P = 0.0001) to the liver metastasis (KMS 25; tumor compared with metastasis, P = 0.0135). We found no correlation between loss of KAI1 expression and stage of disease. In 10 patients, we also noted loss of KAI1 expression in the transition from normal colonic mucosa (KMS 237) to adenoma (KMS 174) to carcinoma (KMS 62; P < 0.0167 for all three comparisons). We conclude that the down-regulation of KAI1 occurs early in the progression of colorectal cancer.
Insights
KAI1 (CD82) expression decreases during colorectal cancer progression, indicating its role as a tumor suppressor. This down-regulation occurs early, from normal tissue to adenoma and carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- KAI1 (CD82) is a transmembrane 4 superfamily member known to inhibit metastasis in prostate cancer and melanoma.
- Reduced KAI1 expression is observed in various adult epithelial cancers, suggesting its involvement in tumor progression.
Purpose of the Study:
- To investigate the expression patterns of KAI1 in the progression of human colorectal cancer.
- To determine if KAI1 down-regulation is an early event in colorectal tumorigenesis.
Main Methods:
- Analysis of KAI1 expression in 20 colorectal cancer cell lines using immunoblotting.
- Immunohistochemical analysis of KAI1 protein expression in 84 patient tissue samples.
- Quantification of KAI1 expression using a KAI1 Mean Score (KMS) based on staining intensity and percentage of positive cells.
Main Results:
- KAI1 expression was heterogeneous in colorectal cancer cell lines, with increased glycosylation in tumor cells.
- KAI1 was significantly down-regulated in primary colorectal tumors (KMS 65) compared to normal colonic mucosa (KMS 226).
- Progressive KAI1 down-regulation was observed from normal mucosa to primary tumors and further to liver metastases in stage IV disease.
- Loss of KAI1 expression was noted during the transition from normal colonic mucosa to adenoma and then to carcinoma.
Conclusions:
- KAI1 down-regulation is an early event in the progression of human colorectal cancer.
- Reduced KAI1 expression may contribute to colorectal cancer development and progression.
- KAI1 serves as a potential biomarker for early colorectal cancer detection and progression.
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