Dual roles of E-cadherin in prostate cancer invasion.
The role(s) of E-cadherin in tumor progression, invasion, and metastasis remains somewhat enigmatic. In order to investigate various aspects of E-cadherin biological activity, particularly in prostate cancer progression, our laboratory cloned unique subpopulations of the heterogeneous DU145 human prostatic carcinoma cell line and characterized their distinct biological functions. The data revealed that the highly invasive, fibroblastic-like subpopulation of DU145 cells (designated DU145-F) expressed less than 0.1-fold of E-cadherin protein when compared to the parental DU145 or the poorly invasive DU145 cells (designated DU145-E). Experimental disruption of E-cadherin function stimulated migration and invasion of DU145-E and other E-cadherin-positive prostate cancer cell lines, but did not affect the fibroblastic-like DU145-F subpopulation. Within the medium of parental DU145 cells, the presence of an 80 kDa E-cadherin fragment was detected. Subsequent functional analyses revealed the stimulatory effect of this fragment on the migratory and invasive capability of E-cadherin-positive cells. These results suggest that E-cadherin plays an important role in regulating the invasive potential of prostate cancer cells through an unique paracrine mechanism.
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242-1109, USA.
Jirapat
J
Chunthapong
Elisabeth A
EA
Seftor
Zhila
Z
Khalkhali-Ellis
Richard E B
RE
Seftor
Sumaira
S
Amir
David M
DM
Lubaroff
Paul M
PM
Heidger
Mary J C
MJ
Hendrix
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015820:Cadherins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin; D000095002:Delta Catenin
D000906:Antibodies; C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D007141:Immunoglobulin Fc Fragments; D010446:Peptide Fragments; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000095002:Delta Catenin