Factors affecting ALCAM/ CD166 expression in breast cancer

A Jezierska^a, WP Olszewski MD^b, J Pietruszkiewicz MD^b, WT Olszewski MD^b, T Motyl Dr^a

^aDepartment of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw, Poland, ^bThe Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is expressed in different kinds of normal and neoplastic tissues. The data on tissue distribution of ALCAM suggest that this protein is involved in a tumour progression and metastasis (e.g. malignant melanoma or prostate cancer). The lack of any data on expression of ALCAM in breast cancer prompted us to undertake the study on involvement of this adhesion molecule in tumour progression and metastases. The relationship between expression ALCAM and expression of estrogen (ER), progesterone (PgR) and cerb-B2 receptors, alpha-catenin, E-cadherin and MMP2 in breast tissue was investigated. The influence of factors affecting breast cancer cell proliferation and survival (17-beta-estradiol, tamoxifen, BCL-2 overexpression and camptothecin) on ALCAM expression and subcellular localization was also examined. Observations were performed on 50 breast cancer cases and breast cancer cell lines: MCF-7 and MDA-MB-231. As a reference cell line HBL-100 was used. Laser scanning cytometry was applied for evaluation of ALCAM and other examined proteins expression. Confocal microscopy was used for the study of coalescence of ALCAM and alpha-catenin, E-cadherin and MMP2. Results of the study revealed that expression of ALCAM/CD166 is higher in ER and PgR positive tumours. Stimulatory effect of 17-beta estradiol on expression of ALCAM was shown in estrogen-dependent MCF-7 cells. On the other hand antiestrogen - tamoxifen diminished ALCAM expression. There was no relationship between expression of cerb-B2 receptors and ALCAM in examined breast cancer tissue sections. A high expression of ALCAM in breast cancer tissue was accompanied by a high expression of alpha-catenin. In breast cancers without metastasis (N0) the ratio of ALCAM to MMP2 expression was usually higher then in metastatic tumours (N1-N4). Apoptosis of breast cancer MCF-7 and MDA-MB-231 cells induced by camptothecin or tamoxifen was associated with formation of large clusters and degradation of ALCAM. Surviving subpopulations of breast cancer cells expressed more ALCAM/CD166, which may indicate its protective effect against apoptotic stimuli. Overexpression of antiapoptotic protein BCL-2 in MCF-7 breast cancer cell lines was accompanied by an increase of ALCAM and decrease of MMP2 expression. In contrast to MCF-7 and MDA-MB-231 breast cancer cells the expression of ALCAM/ in normal breast HBL-100 cells was very low. The following conclusions have been drawn: 1) expression of ALCAM/CD166 is dependent on steroid sex hormones; 2) high expression of ALCAM/CD166 promotes breast cancer cells survival: 3) ALCAM/CD166:MMP2 ratio could be an index of tumour metastatic potential.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 898 (Oncogenesis).