Galectin-4 Expression in Carcinoid Tumors

Abstract

Galectins (Gal) are an evolutionarily conserved family of 15 carbohydrate-binding proteins (lectins) that are widely distributed in normal and neoplastic cells in a wide range of organisms. They have roles in inflammation, cell adhesion, tumor progression, and metastasis. The function and distribution of Gal-3 and Gal-1 are well characterized, but less information is available about Gal-4. Recent studies have localized Gal-4 in the enterochromaffin cells of the porcine and murine small intestine. We examined the expression of Gal-4 in primary and metastatic human ileal carcinoid tumors as well as in carcinoid tumors of the stomach, lung, and rectum. A total of 44 primary and 42 ileal metastatic carcinoid tumors were examined by immunohistochemistry using tissue microarrays (TMA) with monoclonal antibodies to Gal-4, Gal-3, and Gal-1. Pulmonary (n = 7), rectal (n = 6), and gastric (n = 6) carcinoids were examined with larger tissue sections. A total of 18 pancreatic neuroendocrine tumors were also examined with larger tissue sections. Western blots of three ileal carcinoids were also done. Gal-4 was most highly expressed in the ileal carcinoids and the levels of expression tended to be higher in primary ileal carcinoids compared to the metastatic tumors (p = 0.069). All 18 pancreatic neuroendocrine tumors were negative for Gal-1, Gal-3, and Gal-4. Western blot showed a 32 kDa band for Gal-4 in the ileal carcinoids. Gal-3 and Gal-1 were not detected in the metastatic ileal carcinoids by Western blotting. Gastric carcinoids also expressed Gal-4, but very few pulmonary or rectal carcinoids were positive for Gal-4 (p = 0.002). Lower levels of Gal-1 and Gal-3 expression were present in ileal carcinoids compared to primary pulmonary and rectal tumors. These results show a differential distribution of Gal-4 in carcinoid tumors in different locations of the gastrointestinal tract and the lungs.