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 pancreat 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.
Similar content being viewed by others
References
Godwin JD. Carcinoid tumors: an analysis of 2837 cases. Cancer 36:560–569, 1975.
Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer 79:813–829, 1997.
Berge T, Linell F. Carcinoid tumours: frequency in a defined population during a 12 year period. Acta Pathol Microbiol Scand [A] 84:322–330, 1976.
Huflejt ME, Leffler H. Galectin-4 in normal tissues and cancer. Glycoconj J 20:247–255, 2004.
Leffler H, Carlsson S, Hedlund M, Qian Y, Poirier F. Introduction to galectins. Glycoconji J 19:433–440, 2004.
Delacour D, Goyer V, Zanetta JP, et al. Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells. J Cell Biol 169:491–501, 2005.
Patterson R, Wang W, Wang JL. Understanding the biochemical activities of galactin-1 and galactin-3 in the nucleus. Glycoconjugate J 19:499–506, 2004.
Wooters MA, Ropp SL, Erickson AK. Identification of galectin-4 isoforms in porcine small intestine. Biochimie 87:143–149, 2005.
Niepceron E, Simian F, Louisot P, Biol-N'garagba MC. Expression of galectin 4 in the rat small intestine during postnatal development. Biochimie 86:115–118, 2004.
Niepceron E, Simian-Lerme F, Louisot P, Biol-N'agaragba MC. Expression and localization of galectin 4 in rat stomach during postnatal development. Int J Biochem Cell Bio 36:909–919, 2004.
Wooters MA, Hildreth MB, Nelson EA, Erickson AK. Immunohistochemical characterization of the distribution of galactin-4 in porcine small intestine. J Histochem Cytochem 53:197–205, 2005.
Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 7:844–847, 1998.
Jin L, Kulig E, Qian X, et al. Distribution and regulation of proconvertases PC1 and PC2 in human pituitary adenomas. Pituitary 1:187–195, 1999.
Sperry A, Jin L, Lloyd RV. Microwave treatment enhances detection of RNA and DNA by in situ hybridization. Diagn Mol Pathol 5:291–296, 1996.
Lloyd RV, Jin L, Qian X, Kulig E. Aberrant p27kip1 expression in endocrine and other tumors. Am J Pathol 150:401–407, 1997.
Perillo NL, Pace KE, Seilhamer JJ, Baum LG. Apoptosis of T cells mediated by galectin 1. Nature 378:736–739, 1995.
Hokama A, Mizoguchi E, Sugimoto K, et al. Induced reactivity of intestinal CD4+T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation. Immunity 20:681–693, 2004.
Hsu DK, Liu FT. Regulation of cellular homeostasis by galectins. Glycoconj J 19:507–515, 2004.
Danielsen ME, van Deurs B. Galectin-4 and small intestinal brush border enzymes form clusters. Mol Biol Cell 8:2241–2251, 1997.
Chiariotti L, Salvatore P, Frunzio R, Bruni CB. Galectin genes: regulation of expression. Glycoconj J 19:441–449, 2004.
Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer 5:29–41, 2005.
Rabinovich GA. Galectin-1 as a potential cancer target. Br J Cancer 92:1188–1192, 2005.
Nagy N, Legendre H, Andre S, et al. Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting. Cancer 97:1849–1858, 2003.
van den Brûle F, Califice S, Castronovo V. Expression of galectins in cancer: A critical review. Glycoconj J 19:537–542, 2004.
Huflejt ME, Jordan ET, Gitt MA, Barondes SH, Leffler H. Strikingly different localization of galectin-3 and galectin-4 in human colon adenocarcinoma T84 cells. J Biol Chem 272:14294–14303, 1997.
Riss D, Jin L, Qian X, et al. Differential expression of galectin-3 in pituitary tumors. Cancer Res 60:2251–2255, 2003.
Ruebel KH, Jin L, Qian X, et al. Effects of DNA methylation on galectin-3 expression in pituitary tumors. Cancer Res 65:1136–1140, 2005.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rumilla, K.M., Erickson, L.A., Erickson, A.K. et al. Galectin-4 expression in carcinoid tumors. Endocr Pathol 17, 243–249 (2006). https://doi.org/10.1385/EP:17:3:243
Issue Date:
DOI: https://doi.org/10.1385/EP:17:3:243