alpha6 integrin cleavage: sensitizing human prostate cancer to ionizing radiation.
OBJECTIVE
The goal was to determine if prostate tumor cells containing a mutant alpha6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments.


METHODS
Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of alpha6 integrin (PC3N-alpha6-WT) or a mutated non-cleavable form of alpha6 integrin (PC3N-alpha6-RR). The resulting tumor growth before, during and after fractionated doses of IR (3 Gyx10 days) was analyzed using the endpoints of tumor growth inhibition (T/C), tumor growth delay (T-C), tumor doubling time (Td) and tumor cell kill (Log(10) cell kill).


RESULTS
The T/C values were 36.1% and 39.5%, the T-C values were 20.5 days and 28.5 days and the Td values were 5.5 and 10.5 days for the irradiated PC3N-alpha6-WT and PC3N-alpha6-RR cells, respectively. The Log(10) was 1.1 for the PC3N-alpha6-WT cells and 0.8 for the PC3N-alpha6-RR cells. The tumor response to IR was altered in tumors expressing the mutant alpha6 integrin as indicated by a significant increase in tumor growth inhibition, an increase in tumor growth delay, an increase in tumor doubling time and an increase in tumor cell kill.


CONCLUSIONS
Blocking integrin cleavage in vivo may be efficacious for increasing the IR responsiveness of slow growing, pro-metastatic human prostate cancer.
The Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Sangita C
SC
Pawar
Shona
S
Dougherty
Michael E
ME
Pennington
Manolis C
MC
Demetriou
B Dino
BD
Stea
Robert T
RT
Dorr
Anne E
AE
Cress
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009154:Mutation; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous
D017931:DNA Primers; D039503:Integrin alpha6; D011994:Recombinant Proteins