A New Cell Adhesion Mechanism Involving Hyaluronate and CD44

Abstract

Aside from the basic importance of understanding various cell adhesion/interaction mechanisms, these processes may also be informative with respect to malignancy and/or metastasis of tumor cells. During studies of adhesion molecules which may mediate attachment of developing lymphocytes to microenvironmental elements in the bone marrow, we discovered an apparently new cell adhesion mechanism. An adhesion model, comprised of a B lineage hybridoma and a cloned stromal cell line, was used to screen monoclonal antibodies prepared by immunizing with the stromal cells. Four antibodies were selected that inhibited the avid binding between these two cell types and, when purified and added to long term bone marrow cultures, they completely prevented lympho-hemopoiesis. Biochemical and other determinations revealed that these antibodies recognize epitopes on a well studied cell surface glycoprotein, Pgp-1/CD44 (Miyake et al., 1990). Another recently completed study revealed that adhesion between the hybridoma and stromal cells was almost completely dependent on hyaluronate (Miyale et al., submitted). This cell recognition/adhesion mechanism may have general importance and direct binding of cells to hyaluronate was particularly noteworthy with myeloma and hybridoma cells. Thus, hyaluronate recognition by CD44 on such tumor cells could have an influence on growth and metastatic ability.