Galectin-4 As a New Marker for Breast Cancer

Institution: La Jolla Institute for Allergy and Immunology
Investigator(s): Margaret Huflejt, Ph.D. -
Award Cycle: 1997 (Cycle III) Grant #: 3IB-0059 Award: $196,900
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Imaging, Biomarkers, and Molecular Pathology: improving detection and diagnosis

Initial Award Abstract (1997)
The long-term goal of this research is to develop a simple, cost-effective, and broad range screening procedure for the detection of breast cancers using a novel diagnostic marker. In the future, this research could lead to other clinical applications, including treatment.

We have found that a protein called galectin-4 is expressed in non-invasive and invasive breast cancers but not in normal breast cells. The antibody to galectin-4 strongly stained all of the breast cancer tissues we tested, whereas the normal breast cells adjacent to the tumor did not stain. An anti-galectin-4 antibody was able to detect the presence of galectin-4 very specifically. It was possible to detect small nests of tumor cells, or even single tumor cells, in unexpected locations such as fat tissue and among aggregates of tumor associated white blood cells.

The current view in the field of diagnostic surgical pathology is that at least some breast cancers progress through a series of pre-cancerous stages. However, existing methods do not allow for the precise determination of the point at which the pre-cancerous disease becomes cancer. Information about the presence of galectin-4 on a cell might prove extremely useful in helping us to make this distinction. The presence of galectin-4 at an early stage of non-invasive breast disease as well as in invasive cells strongly suggests that this protein is involved in the processes underlying tumor progression. Therefore, in the main project of this research we will investigate the possibility of using galectin-4 as a specific diagnostic marker of breast cancer whose patterns of expression at early stages of disease could identify those patients with a high risk of progression to aggressive cancers. We will use several alternative approaches such as nucleic acid-based probes and immunoblotting to assure correct evaluation of the galectin-4 expression in various types of early breast cancer and in different types of invasive mammary carcinomas. We will also determine whether expression of galectin-4 in presumptive pre-cancer lesions is correlated with the onset of the progression to malignancy.

Our preliminary results show that galectin-4 modulates cellular adhesion. Therefore in the second project we will introduce galectin-4 into cultured "normal" breast epithelial cells that do not express galectin-4 and determine whether this protein can alter the proliferative and migratory properties of breast cells.

Final Report (1999)
The long term goal of this research is to develop a simple, cost effective, and broad range screening procedure for the detection of breast cancers using a novel diagnostic marker. We have initiated this research project after finding that galectin 4 (an endogenous animal lectin) is present in high levels in all in situ and invasive breast cancers but not in normal breast epithelial cells. We were able to detect small nests of tumor cells, or even single tumor cells, in unexpected locations such as fat tissue and aggregates of tumor infiltrating lymphocytes using the galectin-4 marker. Since this project was funded (June 1997) we have made the following progress:

1. In a large study involving collaborations with pathologists from several hospitals we have confirmed that galectin 4 is present in high levels in 100% of in situ carcinomas and in 97% of invasive breast cancers. We have also observed extremely levels of this protein in distinct small groups of cells ("hot spots") in breast tissues of some patients with breast disease currently diagnosed as benign. In parallel study we have found "hot spots" in tissues of all ten patients diagnosed with the benign breast disease but who developed invasive cancers within next 1 4 years. Since we have linked high levels of galectin 4 with abnormal hyper-proliferation of breast epithelium, we are currently testing the possibility (on the larger population of patients) that "hot spots" mark the presence of pre-malignant cells, even in presumably benign tissues of patients, who might be therefore at increased risk of development of malignancy in the near future. If confirmed, this study will help to identify the population of patients at high risk, who should be given special medical attention. Further study of this population should help to develop concepts for the preventive treatments.

2. We have found that another member of galectin family, galectin l, is over expressed in many in situ and invasive breast cancers, but the two galectins 1 and 4 have distinctly different tissue localization. In "normal" breast tissues galectin 1 is often abundant in myoepithelia and in vascular smooth muscles whereas during progression of breast disease galectin 1 is induced in endothelium, stroma, and in epithelial component with intensity highly variable between patients. Since immunosuppressive activity of galectin 1 has been reported in models of autoimmune disorders, we are currently investigating the possibility that induction of galectin 1 is a determinant of tumor immunosuppressive activity.

Effects of Thomsen-Friedenreich antigen-specific peptide P-30 on beta-galactoside-mediated homotypic aggregation and adhesion to the endothelium of MDA-MB-435 human breast carcinoma cells
Periodical:Cancer Research
Index Medicus: Cancer Res
Authors: Glinsky VV, Huflejt ME, Glinsky GV, Deutscher SL, Quinn TP
Yr: 2000 Vol: 60 Nbr: 10 Abs: Pg:2548-8