Expression of hyaluronan receptors CD44 and RHAMM in stomach cancers: relevance with tumor progression

Interactions of hyaluronic acid (HA) with its binding proteins CD44 and RHA MM (receptor for HA-mediating motility) have been proposed to be important in promoting tumor progression and dissemination. However, a comparative st udy of their expression patterns in stomach cancer and its associated lesio ns is not yet available. To address this issue, the combined examinations o f pathology, immunocytochemistry and Western blot hybridization were perfor med on advanced gastric cancer specimens as well as their preneoplastic and non-cancerous counterparts. Alternative CD44 expression was observed in th e gastric mucosa with different lesions. CD44 proteins harboring variant ex on 6 (CD44 v6) was detected only in cancer tissues with a total positive ra te of 14% (10/74). Intracellular RHAMM molecules in Mr 93000 to 95000 were expressed in 3/31 non-cancerous mucosa. RHAMM detection rates increased alo ng with tumor progression. Irrespective of the differences of gross and mor phological pattern, majority (54/74) of cancer cases expressed multiple RHA MM isoforms in Mr 40000-45000, 64000, 70000-73000, 85000 and 93000-95000 wi th the appearance of cell surface immunocytochemical labeling. Among CD44 v ariant isoforms, v6 is more relevant with malignant transformation of gastr ic epithelium. Expression of RHAMM, especially the cell surface variants, i s closely correlated with tumor progression (P<0.01). Expression of CD44 an d RHAMM may benefit the invasion and metastasis of gastric cancer cells pre sumably in a reciprocal manner.