Specific Role of T and Tn Tumor‐associated Antigens in Adhesion between a Human Breast Carcinoma Cell Line and a Normal Human Breast Epithelial Cell Line

Abstract

The possibility that tumor-associated antigens T and Tn act as adhesion molecules between normal and malignant breast epithelial cells at the early stages of recognition in the metastatic pathway was examined in vitro. The adhesive specificity of the antigens was assessed by means of in vitro adhesion tests between a carcinomatous breast cancer cell line (ZR75-30) and a normal epithelial breast cell line (HLB100) using both monoclonal antibodies and lectins specific as well as nonspecific for each antigen. Adhesion assay was performed using monolayers of the normal cell line prepared on plastic culture plates and the tumor cell line labeled with a fluorescent dye as a probe. The adhesion between the two cell types occurred with significant specificity via T and Tn antigens (P < < < <0.001), and was temperature-dependent. The results suggest that at the early stages of recognition by tumor cells in the metastatic process, T and Tn antigens play a role as adhesion molecules between the tumor cells and adjacent normal cells. Key words: Breast carcinoma -Cell line -Adhesion -T and Tn antigensCell-cell interactions are of obvious importance not only in normal physiological processes, but also in the processes of proliferation and invasion of carcinoma (CA) cells, [1][2][3] and metastasis. 4) Several steps in cancer invasion have been investigated. The first step is considered to be the release of cancer cells from the primary cancer lesion due to the regulatory effects of E-cadherin-related systems. 5,6) In the second step, the released cancer cells make contact with nearby normal epithelial cells before reaching the extra-cellular matrix or vascular endothelial cells. This step may be one of the most important in the very early stage of the metastatic processes, such as in the intraductal invasion of breast cancer cells. Little attention, however, has been paid to this event, i.e., the interaction or the binding of malignant cells to healthy (normal) cells immediately after release from the original cancer lesion.Among the tumor-associated antigenic glycoproteins, T [Gal(β1-3)GalNAc(α1-3)Ser/Thr] and Tn [GalNAc(α1-3)-Ser/Thr] antigens were first described as cryptic determinants on human erythrocytes 7) that were exposed by neuraminidase treatment. These pan-CA auto-antigens [8][9][10] play a profound role in cancer pathogenesis. 11) Specific adhesion between invasive, metastatic murine Esb T-lymphoma cells and syngeneic hepatocytes has been demonstrated 12, 13) ; direct molecular binding of the Esb cells, which were later confirmed to strongly express T and Tn antigens on their cell surfaces, 14) to the corresponding ligands was the first step after the recognition of hepatocyte ligands. Moreover, cultured breast CA DU4475 cells and desialylated, isologous erythrocytes [TRBC] bound specifically to the Gal/GalNAc receptors of rat Kupffer cells and of hepatocytes. 15,16) These findings suggest that T and/or Tn antigens on released cancer cells might have a role in adhesion of these cells to normal cells in the early ...

Cancer vaccines and carbohydrate epitopes

“…The potential number of people that could possibly be helped with a vaccine to a target on all of these cancers is staggering. TF-Ag is also a promising target because adhesion mediated by TF-Ag plays a role in metastasis [135,141,142,153,156,157]. This role in metastasis is important because a humoral immune response generated by a vaccine to TF-Ag could kill the tumor cells by ADCC and CDC and in addition could block the ability of the tumor cells to spread.…”

Study of the expression of Tn antigen in different types of human breast cancer cells using VVA-B4 lectin

“…Its widespread presence has been noted on tumors of epithelial origin but it is absent on tumors of ectodermal and mesodermal origin (8). Studies using monoclonal antibodies and lectins have demonstrated the expression of sialylated and nonsialylated forms of Tn antigen in gastrointestinal tumors, particularly in colon cancer (9,10), pancreatic (11) and gastric (12) cancers, in ovarian (13) and uterine (14) cancers, and in numerous cases of breast cancer (14)(15)(16)(17)(18). Tn antigen mostly occurs in malignant breast lesions, invasive carcinomas and their metastases, but it has also been found in benign lesions.…”

An MMP-2/MMP-9 inhibitor, 5a, enhances apoptosis induced by ligands of the TNF receptor superfamily in cancer cells

“…To that end, we tested several other cell lines, including a nontumorigenic transformed breast epithelial cell line (HBL100) 39 and the aggressively metastatic MDA-MB-231 40 breast cancer cell line. We also tested the poorly metastatic melanoma cell line A375P and its metastatic variant melanoma cell line A375SM, 41 and three osteosarcoma cell lines (MG63, SOAS-2, and TA29), a lymphoblastic leukemia (Z119), and four acute mylogenous leukemia cell lines (AML-2, AML-3, KBM5, and KBM7).…”