Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions.
OBJECTIVE
Cell adhesion molecule 1 (CADM1), mediates nerve-mast cell attachment and communication through homophilic binding. An immunohistochemical screen showed that CADM1 is expressed in pancreatic islets. Here, we determined the cell types expressing CADM1 and examined its role in nerve-islet cell interactions.


METHODS
Immunohistochemistry and double-staining immunofluorescence were performed on murine and human pancreases and on islet cell tumors (ICTs). alphaTC6 cells, a murine alpha cell line, were cultured on neurite networks of superior cervical ganglia. Neurite-alphaTC6 cell attachment and communication were examined after nerves were activated specifically by scorpion venom.


RESULTS
CADM1 was expressed on the plasma membrane in all 4 major types of islet cells, alpha, beta, D, and pancreatic polypeptide in human beings, but primarily in alpha cells in mice. In cocultures, alphaTC6 cell to neurite attachment was inhibited dose-dependently by an anti-CADM1 function-blocking antibody. In response to scorpion venom-evoked nerve activation, 36% of the alphaTC6 cells mobilized Ca(2+), and introduction of a CADM1-targeting small interfering RNA reduced the fraction of responding cells to 7%. In 21 human ICTs, CADM1 was present in the plasma membrane of 7, and the others were negative for CADM1. Six of the CADM1-expressing tumors were functional hormonally, whereas all but 2 of the CADM1-negative tumors were nonfunctional (P = .0032).


CONCLUSIONS
CADM1 is a novel islet cell adhesion molecule mediating nerve-islet cell interactions. The strong correlation between CADM1 expression and hormonally functional phenotypes suggests that CADM1 is involved in hormone secretion from ICTs.
Koma
Yu-Ichiro
Y
Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Furuno
Tadahide
T
Hagiyama
Man
M
Hamaguchi
Kazuyuki
K
Nakanishi
Mamoru
M
Masuda
Mari
M
Hirota
Seiichi
S
Yokozaki
Hiroshi
H
Ito
Akihiko
A
D000328:Adult; D000818:Animals; D018273:Carcinoma, Islet Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D005934:Glucagon