The Impact of Stress on Tumor Growth; the Significance of Peripheral Corticotropin Releasing Factor
Final rept. 15 Sep 2007-14 Apr 2009
CRETE UNIV HERAKLION
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Corticotropin Releasing Factor CRF is the major mediator of hypothalamic response to stress. CRF has been detected not only in the central nervous system but also in peripheral tissues and organs and in sympathetic neurons. Even though systemic stress has been reported to affect cancer cell growth primarily due to suppression of the immune response against cancer cells, no information was available on the impact of peripheral CRF on breast cancer. Aim of our studies was to determine the impact of peripheral CRF on breast tumor growth and propose a novel potential mechanism on the crosstalk between the stress-response axis and tumors. The results indicated that CRF induced the expression of beta-catenin and Smad2 affecting Wnt and Tgf-Beta signaling pathways. CRF also induced actin polymerization and stress fiber formation supporting an effect on cell motility. In vivo administration of a CRF antagonist in a mouse mammary tumor model where mice were subjected to chronic stress, indicated that inhibition of CRF resulted in reduced tumor burden, angiogenesis and metastasis in the liver. Overall, the present work supports that CRF mediates stress-induced breast cancer growth and metastasis.
- Medicine and Medical Research