Aberrant
carbohydrate expression frequently occurs in
breast cancer and may endow cells with metastatic potential. Here we first studied the relationship between expression of
Vicia villosa agglutinin (
lectin) (VVA)-binding
carbohydrates and aggressive
breast cancer. We then investigated the molecular characteristics of these
glycoproteins and compared them with those of
glycoproteins recognized by the mouse anti-Tn
monoclonal antibody (MAb) HB-Tn1. Histochemical studies of samples from 322 cases of invasive
ductal carcinoma demonstrated that VVA-binding
carbohydrate expression correlated with
tumor stage, lymphatic invasion, and
lymph node metastasis (p=0.0385, p=0.0019, and p=0.0430. respectively). Western blotting analysis of frozen materials from 39 cases, under denaturing and reducing conditions, revealed that the major
cancer cell-specific VVA-
binding proteins were molecules of about 30, 33, and >200 kDa. Cases expressing the approximately 33 kDa molecule had significant lymphatic invasion more frequently than did cases not expressing this molecule (p=0.0076). Binding of VVA to the approximately 30 and approximately 33 kDa molecules was completely lost by preincubation of VVA with 1 mM
Tn antigen (N-acetylgalactosamine alpha1-O-serine). The VVA-binding molecules appeared to react with VU-3C6 anti-MUC1 MAb. Expression of HB-Tn1 in
breast cancer cells showed significant correlation with expression of VVA-binding
carbohydrate(s) (p<0.0001) but HB-Tn1 reactivity was not clearly related to
breast cancer aggressiveness. Because anti-Tn MAbs bound to
Tn antigen clusters, we concluded that atypical MUC1 bearing the noncluster form of
Tn antigen is implicated in aggressive growth of primary
breast cancer cells, particularly in
lymphatic metastasis.