Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy.
BACKGROUND
Recent studies demonstrated the importance of ADAM9 in prostate cancer relapse upon therapy. In this study, we determined the role of ADAM9 in the therapeutic resistance to radiation and chemotherapy.


METHODS
ADAM9 was either transiently or stably knocked down in C4-2 prostate cancer cells. The sensitivity of ADAM9 knockdown cells toward radiation and chemotherapeutic agents were determined. Additionally, the effects of ADAM9 knockdown on prostate cancer cell morphology, biochemical and functional alterations were accessed.


RESULTS
Both transient and stable knockdown of ADAM9 resulted in increased apoptosis and increased sensitivity to radiation. ADAM9 knockdown also increased prostate cancer sensitivity to several chemotherapeutic drugs. ADAM9 knockdown resulted in increased E-cadherin and altered integrin expression and underwent phenotypic epithelial transition. These were reflected by the morphological, biochemical, and functional alterations in the ADAM9 knockdown cells.


CONCLUSIONS
ADAM9 plays a crucial role in prostate cancer progression and therapeutic resistance in part by altering E-cadherin and integrin expression. ADAM9 is an important target for the consideration of treating prostate cancer patients who developed therapeutic resistance and disease relapse.
Josson
Sajni
S
Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. sajni.josson@cshs.org
Anderson
Cynthia S
CS
Sung
Shian-Ying
SY
Johnstone
Peter A S
PA
Kubo
Hiroyuki
H
Hsieh
Chia-Ling
CL
Arnold
Rebecca
R
Gururajan
Murali
M
Yates
Clayton
C
Chung
Leland W K
LW
D051722:ADAM Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015820:Cadherins / Q000032:analysis; D045744:Cell Line, Tumor; D004848:Epithelium / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011836:Radiation Tolerance; D013481:Superoxides / Q000032:analysis
D015820:Cadherins; D016023:Integrins; D008565:Membrane Proteins; D013481:Superoxides; D051722:ADAM Proteins; C098339:ADAM9 protein, human