Alpha 1 and alpha 2 Ca2+ channel subunit expression in human neuronal and small cell carcinoma cells.
Monoclonal antibodies that recognize skeletal muscle dihydropyridine-sensitive calcium channel subunits were used to identify similar proteins in neuronal and small cell carcinoma cell lines. alpha 1-related proteins were detected by FACS analysis on the surface of human neuroblastoma (IMR 32) and small cell carcinoma (DMS 273 and DMS 114) cell lines. alpha 1-like polypeptides from these cells were isolated and partially characterized. The polypeptides exhibit an M(r) similar to that of the L-type channel alpha 1 subunit and are recognized by two distinct anti-alpha 1 mAbs. The data provide biochemical evidence for structural similarities between the alpha 1 subunit of small cell carcinoma and neuronal cell lines. Similarly, an alpha 2-like protein was characterized from these cells. Because alpha 2 is a subunit shared by many subtypes of calcium channels, these data suggest that subunits other than the pore-forming alpha 1 subunit may play an important role in the etiology of Lambert-Eaton syndrome. We demonstrate directly that small cell carcinoma and a cell line derived from peripheral neurons share L-type calcium channel-related proteins and a protein common to many voltage-gated calcium channel subtypes. These data support a model that proposes that cross-reactivity of anti-tumor cell antibodies with presynaptic elements, possibly calcium channels, plays a role in the development of Lambert-Eaton syndrome.
Morton
M E
ME
Department of Biology, College of the Holy Cross, Worcester, Massachusetts 01610.
Cassidy
T N
TN
Froehner
S C
SC
Gilmour
B P
BP
Laurens
R L
RL
D000911:Antibodies, Monoclonal; D015220:Calcium Channels / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D018288:Carcinoma, Small Cell; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms; D046911:Macromolecular Substances; D009447:Neuroblastoma; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D046911:Macromolecular Substances