Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients.
S100P, an EF-hand calcium-binding protein, has been reported to be associated with the progression of many types of cancers. Transfection of an expression vector for S100P into a benign, nonmetastatic rat mammary cell line causes a 4- to 6-fold increase in its level in all four transformant cell clones. When the resultant transformant cell lines are introduced in turn into the mammary fat pads of syngeneic Furth-Wistar rats, there is a significant 3-fold increase in local muscle invasion and a significant induction of metastasis in 64% to 75% of tumor-bearing animals. In a group of 303 breast cancer patients followed for up to 20 years, antibodies to S100P immunocytochemically stain 161 primary tumors. Survival of patients with S100P-positive carcinomas is significantly worse by about 7-fold than for those with negatively stained carcinomas. There is also a significant association between the class level of immunocytochemical staining of the carcinoma cells and decreased patient survival. Positive staining for S100P is significantly associated with that for two other metastasis-inducing proteins, S100A4 and osteopontin. Patients with tumors that stained positively for both S100P and S100A4 have a significantly reduced survival of 1.1% over patients with either S100 protein alone. Multivariate regression analysis identifies S100P, S100A4, and osteopontin as the most significant independent indicators of death in this group of patients. These results suggest that stratification of patients into groups according to expression of multiple metastasis-inducing proteins may lead to a more accurate prediction of patient survival.
Wang
Guozheng
G
Cancer and Polio Research Fund Laboratories, School of Biological Sciences, University of Liverpool, Liverpool L69 3BX, United Kingdom. wangg@liv.ac.uk
Platt-Higgins
Angela
A
Carroll
Joe
J
de Silva Rudland
Suzete
S
Winstanley
John
J
Barraclough
Roger
R
Rudland
Philip S
PS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000917:Antibody Formation; D001943:Breast Neoplasms / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000032:analysis*; D053495:Osteopontin; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis; D016019:Survival Analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C103003:S100P protein, human; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; C077591:S100A4 protein, human