Several of the
beta1 integrin receptors [very late antigen (VLA) molecules] for extracellular matrix (ECM)
proteins are expressed by malignant T cells in
cutaneous T-cell lymphoma (CTCL). We evaluated the function of
VLA-1, a
beta1 integrin specifically expressed in epidermotropic
mycosis fungoides (MF), in CD4+ leukemic T cells Jurkat line). We found that Jurkat cells adhere significantly to
collagens only after their activation with
phorbol 12-
myristate 13-
acetate (PMA). However, the adhesion to
collagen IV (but not to
collagen I) of Jurkat cells selected for expressing increased levels of VLA-1 (with unchanged levels of
VLA-2, the second
collagen integrin receptor) was significantly enhanced relative to that of "VLA-1 low" cells.
Monoclonal antibody (mAb) 1B3.1, directed against the
collagen binding domain of VLA-1, inhibited adhesion to
collagen IV and to
collagen I by 36.67%+/-5.25% and 18%+/-4.32%, respectively (p<0.05), whereas the inhibition by anti-
VLA-2 mAb PIE6 was comparable on both
collagens (25%+/-7.48% and 36.3%+/-0.94%, respectively; p<0.09). Immuno-histochemical studies of skin biopsies from 10 untreated MF patients showed that in all cases at least 10% of the lymphocytes residing in the epidermis are VLA-1+VLA-2-. While not directly applicable to MF, the demonstrated functions of VLA-1 in leukemic Jurkat cells, together with its expression in MF skin, suggest a role for VLA-1
integrins in epidermotropism in a small proportion of leukemic MF cells.