Corticotropin Releasing Factor promotes breast cancer cell motility and invasiveness.
BACKGROUND
Cancer cells secrete bioactive peptides that act in an autocrine or paracrine fashion affecting tumor growth and metastasis. Corticotropin-releasing factor (CRF), a hypothalamic neuropeptide that controls the response to stress, has been detected in breast cancer tissues and cell lines. CRF can affect breast cancer cells in an autocrine or paracrine manner via its production from innervating sympathetic neurons or immune cells.


METHODS
In the present study we report our findings regarding the impact of CRF on breast cancer cell motility and invasiveness. For this purpose we used the MCF7 breast cancer cell line and evaluated the effect of CRF on motility and invasiveness using the wound-healing and boyden-chamber assays. In addition, we measured the effect of CRF on molecules that mediate motility by western blot, immunofluorescence, ELISA and RT-PCR.


RESULTS
Our findings show that: 1. CRF transiently inhibited the apoptosis of MCF7 cells. 2. CRF enhanced MCF7 cell motility in a wound healing assay and their invasiveness through extracellular matrix. 3. CRF increased actin polymerization, phosphorylation of Focal Adhesion Kinase (FAK), providing a potential mechanism for the observed induction of MCF7 motility. 4. CRF induced the expression of Cox-1 but not Cox-2 in MCF7 cells as well as the production of prostaglandins, factors known to promote invasiveness and metastasis.


CONCLUSIONS
Overall, our data suggest that CRF stimulates cell motility and invasiveness of MCF7 cells most probably via induction of FAK phosphorylation and actin filament reorganization and production of prostaglandins via Cox1. Based on these findings we postulate that the stress neuropeptide CRF present in the vicinity of tumors (either produced locally by the tumor cells themselves or by nearby normal cells or secreted from the innervations of surrounding tissues) may play an important role on breast tumor growth and metastatic capacity, providing a potential link between stress and tumor progression.
Androulidaki
Ariadne
A
Department of Clinical Chemistry, School of Medicine, University of Crete, Heraklion 71003, Crete, Greece. arandrou@med.uoc.gr
Dermitzaki
Erini
E
Venihaki
Maria
M
Karagianni
Effie
E
Rassouli
Olga
O
Andreakou
Erini
E
Stournaras
Christos
C
Margioris
Andrew N
AN
Tsatsanis
Christos
C
D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011453:Prostaglandins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D011453:Prostaglandins; D003346:Corticotropin-Releasing Hormone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human