Identification of a Novel Structural Variant of the α₆ Integrin

The α₆ integrin is a 140-kDa (nonreduced) laminin receptor. We have identified a novel 70-kDa (nonreduced) form of the α₆ integrin called α₆p for the latin word parvus, meaning small. The variant was immunoprecipitated from human cells using four different α₆-specific monoclonal antibodies but not with α₃ or α₅ antibodies. The α ₆p integrin contained identical amino acid sequences within exons 13-25, corresponding to the extracellular "stalk region" and the cytoplasmic tail of the α₆ integrin. The light chains of α₆ and α₆p were identical as judged by α₆A-specific antibodies and electrophoretic properties. The α₆p variant paired with either β₁ or β₄ subunits and was retained on the cell surface three times longer than α₆. Reverse transcription/polymerase chain reaction analysis revealed a single polymerase chain reaction product. The α₆p variant was found in human prostate (DU145H, LnCaP, PC3) and colon (SW480) cancer cell lines but not in normal prostate (PrEC), breast cancer (MCF-7), or lung cancer (H69) cell lines or a variant of a prostate carcinoma cell line (PC3-N). Protein levels of α₆p increased 3-fold during calcium-induced terminal differentiation in a normal mouse keratinocyte model system. A novel form of the α₆ integrin exists on cell surfaces that contains a dramatically altered extracellular domain.