ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy.
BACKGROUND
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a 105-kDa transmembrane glycoprotein linked with cell migration and development and with cancer progression (malignant melanoma, prostate cancer and, very recently, breast cancer). This report is the first evaluation of ALCAM/CD166 in an estrogen-dependent (MCF-7) and a metastatic (MDA-MB-231) breast cancer cell line and a reference breast cell line (HBL-100). The effects of estrogen and anti-estrogen treatment, bcl-2 overexpression, and ALCAM gene silencing on ALCAM/CD166 protein concentration and cell survival were investigated.


METHODS
Laser scanning cytometry, confocal microscopy, and Western blotting were used for the determination of ALCAM/CD166 protein and biochemical markers of apoptosis and autophagy.


RESULTS
17-beta-estradiol increased and tamoxifen inhibited ALCAM/CD166 expression and survival of MCF-7 cells. Overexpression of the bcl2 gene in MCF-7 bcl2/neo, MDA-MB-231 bcl2/neo, and HBL-100 bcl2/neo cells significantly increased ALCAM/CD166 expression and was accompanied by decreasing MMP-2 concentrations. Appearance of the ALCAM/CD166 protein was noted in HBL-100 bcl2/neo in contrast to an almost undetectable level in HBL-100 cells. ALCAM gene silencing in MCF-7 cells decreased the concentration of BCL-2 and increased levels of apoptosis (89-kDa PARP, active caspase7) and autophagy (MAP1LC3, Beclin1) markers.


CONCLUSIONS
The above results indicate that ALCAM-ALCAM interactions are crucial to the survival and primary site maintenance of breast cancer cells. Impaired expression of ALCAM/CD166 is associated with the induction of two types of programmed cell death, apoptosis and autophagy, in breast cancer cells. This adhesion molecule can therefore be regarded as a potential novel breast cancer indicator and therapeutic target.
Jezierska
Agnieszka
A
Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw, Poland. agnieszkajezierska@poczta.onet.pl
Matysiak
Wojciech
W
Motyl
Tomasz
T
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013629:Tamoxifen; D004958:Estradiol; D020778:Matrix Metalloproteinase 2