α6 Integrin Cleavage: Sensitizing human prostate cancer to ionizing radiation

Sangita C. Pawar, Shona Dougherty, Michael E. Pennington, Manolis C. Demetriou, Baldassarre Stea, Robert T Dorr, Anne E Cress

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose: The goal was to determine if prostate tumor cells containing a mutant α6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments. Material and methods: Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of α6 integrin (PC3N-α6-WT) or a mutated non-cleavable form of α6 integrin (PC3N-α6-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 (Log10 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-α6-WT and PC3N-α6-RR cells, respectively. The Log10 was 1.1 for the PC3N-α6-WT cells and 0.8 for the PC3N-α6-RR cells. The tumor response to IR was altered in tumors expressing the mutant α6 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.

Original languageEnglish (US)
Pages (from-to)761-767
Number of pages7
JournalInternational Journal of Radiation Biology
Volume83
Issue number11-12
DOIs
StatePublished - 2007

Fingerprint

sensitizing
Ionizing radiation
integrins
prostatic neoplasms
Ionizing Radiation
ionizing radiation
Integrins
Tumors
cleavage
Prostatic Neoplasms
tumors
cancer
neoplasms
Neoplasms
Cells
Growth
cells
growth retardation
mutants
endpoints

Keywords

  • Growth delay
  • Integrin
  • Ionizing radiation
  • Prostate cancer
  • Tumor cell kill
  • Tumor doubling time
  • Tumor growth inhibition

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Nuclear Energy and Engineering
  • Radiation

Cite this

α6 Integrin Cleavage : Sensitizing human prostate cancer to ionizing radiation. / Pawar, Sangita C.; Dougherty, Shona; Pennington, Michael E.; Demetriou, Manolis C.; Stea, Baldassarre; Dorr, Robert T; Cress, Anne E.

In: International Journal of Radiation Biology, Vol. 83, No. 11-12, 2007, p. 761-767.

Research output: Contribution to journalArticle

Pawar, Sangita C. ; Dougherty, Shona ; Pennington, Michael E. ; Demetriou, Manolis C. ; Stea, Baldassarre ; Dorr, Robert T ; Cress, Anne E. / α6 Integrin Cleavage : Sensitizing human prostate cancer to ionizing radiation. In: International Journal of Radiation Biology. 2007 ; Vol. 83, No. 11-12. pp. 761-767.
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abstract = "Purpose: The goal was to determine if prostate tumor cells containing a mutant α6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments. Material and methods: Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of α6 integrin (PC3N-α6-WT) or a mutated non-cleavable form of α6 integrin (PC3N-α6-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 (Log10 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-α6-WT and PC3N-α6-RR cells, respectively. The Log10 was 1.1 for the PC3N-α6-WT cells and 0.8 for the PC3N-α6-RR cells. The tumor response to IR was altered in tumors expressing the mutant α6 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.",
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AU - Pawar, Sangita C.

AU - Dougherty, Shona

AU - Pennington, Michael E.

AU - Demetriou, Manolis C.

AU - Stea, Baldassarre

AU - Dorr, Robert T

AU - Cress, Anne E

PY - 2007

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N2 - Purpose: The goal was to determine if prostate tumor cells containing a mutant α6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments. Material and methods: Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of α6 integrin (PC3N-α6-WT) or a mutated non-cleavable form of α6 integrin (PC3N-α6-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 (Log10 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-α6-WT and PC3N-α6-RR cells, respectively. The Log10 was 1.1 for the PC3N-α6-WT cells and 0.8 for the PC3N-α6-RR cells. The tumor response to IR was altered in tumors expressing the mutant α6 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.

AB - Purpose: The goal was to determine if prostate tumor cells containing a mutant α6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments. Material and methods: Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of α6 integrin (PC3N-α6-WT) or a mutated non-cleavable form of α6 integrin (PC3N-α6-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 (Log10 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-α6-WT and PC3N-α6-RR cells, respectively. The Log10 was 1.1 for the PC3N-α6-WT cells and 0.8 for the PC3N-α6-RR cells. The tumor response to IR was altered in tumors expressing the mutant α6 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.

KW - Growth delay

KW - Integrin

KW - Ionizing radiation

KW - Prostate cancer

KW - Tumor cell kill

KW - Tumor doubling time

KW - Tumor growth inhibition

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