Integrin alpha 6 is a differentiation antigen of human granulosa cells.

We previously reported a new murine monoclonal antibody (mAb), OG-1, raised against human granulosa cells (GC) and showed that the OG-1 antigen is a cell surface differentiation-related molecule expressed on GC of follicles and on large luteal cells in the early to midluteal phase. In this study, we further characterized the OG-1 antigen. An immunohistochemical study showed that the OG-1 antigen was also expressed on endometrial glandular and stromal cells and on first trimester and term placental trophoblasts. The antigen purified from endometrium, chorionic villi, or placenta by immunoaffinity chromatography using the mAb OG-1 consisted of a 120-kilodalton (kDa) protein. Partial amino acid sequencing of the 120-kDa protein purified from placenta revealed that the 16 amino acids from the N-terminus were identical to those of the heavy chain of human integrin alpha 6, the molecular mass of which is reportedly 118-126 kDa. We examined the tissue distribution of integrins alpha 6, beta 1, and beta 4, because integrin alpha 6 forms heterodimers with integrins beta 1 or beta 4. Indirect immunofluorescence staining of various follicles and corpora lutea using two known antiintegrin alpha 6 monoclonal antibodies (450-30A1 and GoH3) showed that integrin alpha 6 was expressed on granulosa and large luteal cells in a profile similar to that of the OG-1 antigen. Integrin beta 1 was expressed on granulosa and large luteal cells, but integrin beta 4 was undetectable. Integrin beta 1 was also expressed on thecal and stromal cells. In term placentas, the OG-1 antigen and integrins alpha 6 and beta 4 were expressed on trophoblasts, whereas integrin beta 1 was expressed on villous capillary endothelia. These results indicate that the mAb OG-1 recognizes integrin alpha 6, and that integrin alpha 6 is a differentiation-related antigen of human GC, suggesting the involvement of integrins in human folliculogenesis and luteal formation.