alpha6 integrin cleavage: sensitizing human prostate cancer to ionizing radiation.

Abstract

PURPOSE:

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.

MATERIAL AND 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.

• Authors: Sangita C Pawar, Shona Dougherty, Michael E Pennington, Manolis C Demetriou, B Dino Stea, Robert T Dorr, Anne E Cress
• Journal: International journal of radiation biology (Int J Radiat Biol) 2007 Nov-Dec Vol. 83 Issue 11-12 Pg. 761-7 ISSN: 0955-3002 [Print] England
• PMID: 18058365 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• DNA Primers
• Integrin alpha6
• Recombinant Proteins

Topics

• Animals
• Base Sequence
• Cell Line, Tumor
• DNA Primers (genetics)
• Humans
• Integrin alpha6 (genetics, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Mutation
• Neoplasm Transplantation
• Prostatic Neoplasms (genetics, metabolism, pathology, radiotherapy)
• Radiation Tolerance (genetics, physiology)
• Recombinant Proteins (genetics, metabolism)
• Transfection
• Transplantation, Heterologous