Cellular localization of CD44 correlates with cell proliferation and liver metastasis in colon cancer

Background. The functional heterogeneity of the cell adhesion molecule family CD44 is explained by differences in its activity, which is regulated by alterations in the distribution of its cellular localization. The aim of the current study was to evaluate the functional differences in cancer cells according to variations in the cellular localization of CD44. Methods. Paraffin-embedded tissue sections of 34 colon cancers (obtained from 17 patients with liver metastasis and 17 without liver metastasis) were investigated. These tumors were classified according to the predominant pattern of cellular localization of CD44 (the isoforms CD44H, CD44v6, and CD44v9). For each CD44 isoform, the functional differences were investigated for a correlation between localization patterns and Ki-67 labeling index (to indicate cell proliferative activity), and for a correlation between localization patterns and liver metastasis. Results. On staining for CD44H, tumors displayed three localization patterns. One pattern, in which CD44H was expressed on the basal or basolateral side of the plasma membrane in cancer cells, showed a higher Ki-67 labeling index than other localization patterns (P < 0.01), and a higher rate of the basolateral localization pattern was observed in patients with liver metastasis than in those without (P = 0.02). On staining for CD44v6 and CD44v9, tumors showed four and three localization patterns, respectively. No significant differences in localization patterns were found in analyses of the Ki-67 labeling index and liver metastasis for either CD44v6 or CD44v9. Conclusions. A functional correlate of CD44H localization patterns was detected. In particular, cancer cells in which CD44H was localized at the basal or basolateral membranes were closely associated with high proliferative activity and high liver metastatic potential. Received: February 27, 1998 / Accepted: November 16, 1998