Human MUC1 mucin: a multifaceted glycoprotein

Human MUC1 mucin, a membrane-bound glycoprotein, is a major component of th e ductal cell surface of normal glandular cells. MUC1 is overexpressed and aberrantly glycosylated in carcinoma cells. The role MUC1 plays in cancer p rogression represents two sides of one coin: on the one hand, loss of polar ity and overexpression of MUC1 in cancer cells interferes with cell adhesio n and shields the tumor cell from immune recognition by the cellular arm of the immune system, thus favoring metastases; on the other hand, MUC1, in e ssence a self-antigen, is displaced and altered in malignancy and induces i mmune responses. Tumor-associated MUC1 has short carbohydrate sidechains an d exposed epitopes on its peptide core; it gains access to the circulation and comes into contact with the immune system provoking humoral and cellula r immune responses. Natural antibodies to MUC1 present in the circulation o f cancer patients may be beneficial to the patient by restricting tumor gro wth and dissemination: early stage breast cancer patients with a humoral re sponse to MUC1 have a better disease-specific survival. Several MUC1 peptid e vaccines, differing in vectors, carrier proteins and adjuvants, have been tested in phase I clinical trials. They are capable of inducing predominan tly humoral responses to the antigen, but evidence that these immune respon ses may be effective against the tumor in humans is still scarce.