Coexpression of Ganglioside Antigen Fuc-GM1, Neural-Cell Adhesion Molecule, Carcinoembryonic Antigen, and Carbohydrate Tumor-Associated Antigen CA 50 in Lung Cancer

Abstract

With the aid of specific monoclonal antibodies, tumor tissues from 68 patients with lung cancer were examined for their expression of two small cell lung carcinoma (SCLC) antigens, Fuc-GMl (fucosyl GM1; IV²FucII³NeuAc GgOse₄) and neural-cell adhesion molecule (NCAM), and two broader tumor antigens, carcinoembryonic antigen (CEA) and carbohydrate cancer-associated antigen CA 50. Expression of Fuc-GMl was seen in 75% and NCAM in 78% of the SCLC specimens, but also in 12 and 20% of non-SCLC. Either or both of these antigens were expressed in more than 90% of SCLC and in 25% of non-SCLC. CEA was found in more than 80% of SCLC and non-SCLC. Expression of CA 50 was seen in 65–68% of non-SCLC and SCLC, showing preference for SCLC and lung adenocarcinoma. In SCLC, cellular expression of Fuc-GM1 was generally seen together with NCAM and CA 50, but rarely with CEA. There was considerable inter- and intratumor heterogeneity in the expression of all four antigens. The results suggest that CEA is the antigen of choice for the detection of lung cancer regardless of histotype. In combined analysis of CEA, CA 50, Fuc-GM1 and NCAM, two patterns of antigen expression were recognized that appear to discriminate between SCLC and non-SCLC tumors, respectively. A considerable fraction of SCLC and non-SCLC tumors, however, exhibited similar patterns of antigen expression. The biological and clinical significance of these observations remains to be investigated.

The molecular pathogenesis of small cell lung cancer

“…95 Fucosyl GM-1 is a ganglioside that has been found to be expressed in 75% of SCLC specimens, and rarely in normal tissue or NSCLC and other tumors. 96 Polysialic acid, a component of embryonic NCAM, is a polymer of more than twenty negatively-charged alpha 2-8 linked sialic acid residues, which is involved in cell motility and development. It is expressed abundantly in SCLC and not in normal tissues.…”

Advancing immunotherapy in small cell lung cancer

“…Another differentially expressed target on SCLC cells is Fucosyl‐GM1 (FucGM1), a complex glycosphingolipid with a carbohydrate chain 34,35 . FucGM1 is normally expressed in the dorsal root ganglia and peripheral sensory neurons, where it functions in cell–cell adhesion and signal transduction 36 .…”

“…33 Another differentially expressed target on SCLC cells is Fucosyl-GM1 (FucGM1), a complex glycosphingolipid with a carbohydrate chain. 34,35 FucGM1 is normally expressed in the dorsal root ganglia and peripheral sensory neurons, where it functions in cell-cell adhesion and signal transduction. 36 Preclinical studies have shown that targeting FucGM1 can harness the innate immune system via binding of the FcγRIIIa (CD16), leading to antibody-dependent cellular cytotoxicity as well as complement-mediated cytotoxicity and antibody-dependent cellular phagocytosis.…”

Novel Therapeutic Approaches for Small Cell Lung Cancer: The Future has Arrived

“…Fucosyl GM-1 is a ganglioside expressed in 75% of SCLC specimens, but only rarely in normal tissue or NSCLC and other tumors [83]. N-proprionylated polysialic acid, a component of embryonic neural cell adhesion molecule, is a polymer of more than twenty negatively-charged alpha 2-8 linked sialic acid residues, which is involved in cell motility and development.…”