Involvement of carbohydrate antigen sialyl Lewisx in... : Diseases of the Colon & Rectum (original) (raw)

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Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis

Nakamori, Shoji M.D.1; Kameyama, Masao M.D.1; Imaoka, Shingi M.D.1; Furukawa, Hiroshi M.D.1; Ishikawa, Osamu M.D.1; Sasaki, Yo M.D.1; Izumi, Yuki M.S.2; Irimura, Tatsuro Ph.D.2

1 Department of Surgery

Osaka Medical Center for Cancer and Cardiovascular Diseases

3-1-1 Nakamichi, Higashinari-Ku

537

Osaka

Japan

2 Department of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Science

The University of Tokyo

Tokyo

Japan

Supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a New 10-Year Strategy for Cancer Control, Japan. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.

Abstract

PURPOSE:

Recognition of metastatic tumor cells with distinct biochemical phenotypes predominant in the primary tumors should be useful not only for establishment of new therapeutic approaches but also for identification of highrisk or low-risk patients for relapse. We examined whether carbohydrate antigens, sialyl Lewisx (sLex) and sialyl Lewisa (sLea) are involved in colorectal cancer metastasis.

METHODS:

Metastatic abilities of human colon cancer cell variants that were selected for their high or low cell surface levels of sLex (KM12-HX and KM12-LX, respectively) were analyzed. Also, immunohistochemical expressions of sLex and sLea in 159 primary colorectal cancers were examined to determine the clinical significance of increased expression of these antigens.

RESULTS:

KM12-HX cells adhered more readily to tumor necrosis factor-α activated endothelial cells than did KM12-LX cells. Increased adhesion of KM12-HX cells to activated endothelial cells was inhibited by antibodies against E-selectin and sLex and by modification of cell surface carbohydrates. KM12-HX cells showed more invasive ability in vitro and more metastatic potential in the liver of nude mice than KM12-LX cells. Although no difference was seen in the expression of six messenger ribonucleic acids corresponding to progression or metastasis of colorectal cancer, expression of fucosyltransferase was found to be responsible for the higher expression of sLex in KM12-HX cells. Clinical records of patients showed that disease-free survival rate of patients with sLex-positive tumors was significantly poorer than that of those with sLex-negative tumors. Cox's multivariate analysis revealed that the sLex status was an independent predictive factor for disease recurrence ( P = 0.004), depth of invasion (P = 0.0005), and histologic type> (P = 0.037 ), but sLea status, age, gender, tumor location, N stage, and vessel invasion were not.

CONCLUSION:

Increased expression of sLex could be involved in establishment of colorectal cancer metastasis. It appears that examining sLex expression may serve as a potent marker of the recurrence in patients with colorectal cancer.