Integrin beta1-mediated invasion of human breast cancer cells: an ex vivo assay for invasiveness.
BACKGROUND
The integrin cell adhesion molecule (CAM) family is intimately involved in cell adhesion and invasion through tissue basement membranes (BM). As a consequence of the short survival of patient-derived human breast cancer cells, the invasion of such cells has not been previously reported. Our aims were to optimise culture conditions in order to establish a reliable invasion assay and to assess the effect on invasion of perturbations of the beta1 integrin receptors.


METHODS
Pure suspensions of viable carcinoma cells were isolated immunomagnetically from human breast cancer (HBC) samples and introduced onto a replicated glycoprotein BM within an invasion chamber. Degree of invasion was compared to both beta1 integrin expression and tumour grade. Additionally, the effect of beta1 receptor blockade with monoclonal antibody (mAb) was assessed.


RESULTS
Invasion was significantly greater in grade II than grade III tumour cells (p=0.0012). Anti-integrin beta1 monoclonal antibody inhibited cancer cell invasion by a mean of 83.96 +/- 4.80%.


CONCLUSIONS
The invasion assay confirmed the fundamental importance of beta1 integrin receptors to transmembrane invasion and reports this for the first time in cells isolated from primary breast cancer. It represents a potent research tool for investigation of the tumour biology of invasion at the integrin beta1-mediated cell-basement membrane interface. This assay has the potential clinical application of improved stratification of patients for adjuvant therapy on a more individual basis than currently available.
Berry
M G
MG
Department of Surgery, St. Bartholomew's and the Royal London School of Medicine and Dentistry, St. Bartholomew's Hospital, UK.
Goode
Anthony W
AW
Puddefoot
John R
JR
Vinson
Gavin P
GP
Carpenter
Robert
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D002478:Cells, Cultured / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019012:Integrin beta1