ErbB-4 may control behavior of prostate cancer cells and serve as a target for molecular therapy.
OBJECTIVE
To assess ErbB-4 expression in advanced human prostate cancer (PC) cell lines, the role of ErbB-4 in motility, migration, and proliferative/tumorigenic potential of PC cells, and efficacy of anti-ErbB-4 monoclonal antibody (Mab) treatment on PC cells in vitro and tumor growth in vivo.


METHODS
Established advanced human PC cell lines (PC-3, Cl-1, and Du-145) were evaluated for ErbB-4 expression. Several Cl-1 cell line clones expressing various levels of ErbB-4 were isolated, their motility, migration capacity, and in vitro proliferation as well as survival following Mab treatment were evaluated. Tumorigenicity and proliferation capacity of these clones in vivo and efficacy of Mab treatment on tumor growth were estimated by measurements of subcutaneous tumors developed in nude mice.


RESULTS
PC cell lines studied express ErbB-4. Both PC-3 and Du-145 cell lines express high ErbB-4 levels; only 50% of Cl-1 cells express ErbB-4 with large heterogeneity. Cl-1 sub-clones highly expressing ErbB-4 showed increased cell motility, migration, and proliferation rate in vitro and enhanced growth in vivo, compared to clones with low ErbB-4 expression. Mab treatment inhibited the growth of cells expressing high but not low ErbB-4 levels in vitro and decreased the growth of subcutaneous tumors in nude mice generated by ErbB-4 highly expressing cells.


CONCLUSIONS
High expression of ErbB-4 in prostate cancer Cl-1 cell clones correlated with high proliferative and migration capacity and high tumorigenic potential. The inhibitory effect of Mab on cell proliferation and on subcutaneous tumor growth suggests ErbB-4's potential as a target for molecular anticancer therapy.
Ben-Yosef
Rami
R
Department of Oncology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. ramiby@post.tau.ac.il
Starr
Alex
A
Karaush
Victoria
V
Loew
Vered
V
Lev-Ari
Shahar
S
Barnea
Itay
I
Lidawi
Ghalib
G
Shtabsky
Alexander
A
Greif
Yoel
Y
Yarden
Yosef
Y
Vexler
Akiva
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005562:Formazans / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018739:Oncogene Proteins v-erbB / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D005562:Formazans; D018739:Oncogene Proteins v-erbB; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan