Loss of KAI1 expression in the progression of colorectal cancer

The transmembrane 4 superfamily member KAL1 (CD82) has been shown to inhibi t pulmonary metastases in experimental metastasis models of prostate cancer and melanoma, KAI1 expression is decreased in the progression of common so lid epithelial tumors of adulthood, including lung, prostate, breast, esoph ageal, gastric, pancreatic, and bladder cancers. The purpose of our study w as to investigate KAI1 expression in the progression of human colorectal ca ncer. We first analyzed 20 colorectal cancer cell lines by immunoblot techn iques. KAI1 was expressed heterogeneously, with the tumor cell Lines having a more complex degree of glycosylation compared with that of the normal co lonic tissue. KAI1 was highly expressed in the primary SW480 colon cancer c ell line but was down-regulated 15-fold in the matched metastatic SW620 cel l line. We also investigated KAI1 protein expression by immunohistochemistr y in tissues from 84 patients with colorectal cancer. Each tissue section w as assigned a KAI1 mean score (KMS) from 0 to 300 based on the product of t he 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 patien ts with stage TV metastatic disease, we observed a progressive down-regulat ion of KAtI1, from the normal adjacent colonic mucosa (KMS 193) to the prim ary tumor (KMS 72; P = 0.0001) to the liver metastasis (KMS 25; tumor compa red with metastasis, P = 0.0135). We found no correlation between toss of K AI1 expression and stage of disease. In 10 patients, we also noted loss of KAI1 expression in the transition from normal colonic mucosa (KR IS 237) to adenoma (KMS 174) to carcinoma (KMS 62; P < 0.0167 for all three compariso ns). We conclude that the down-regulation of KAI1 occurs early in the progr ession of colorectal cancer.