The Role of SDF-1alpha/CXCR4/MMP in PC Bone Metastasis
Abstract
Chemokines and chemokine receptor interactions facilitate the physiological migration of cells. Interaction of chemokines with their receptors leads to the expression/activation of adhesion molecules and proteases. Recent evidence suggests that a similar mechanism may be active in cancer metastasis. Herein, we hypothesize that CxCLl2 and CxCR4 interactions facilitates the metastasis of prostate cancer cells by activating intracellular signaling pathways leading to the expression and release of MMP-9. Using a variety of methods including RT-PCR, ELISA, gelatin zymography, cellular motility and invasion and subcellular fractionation of prostate cancer cells, we showed that (a) bone stromal cells and bone tissue conditioned media induced the migration of PC-3 cells in a CxCR4 dependent manner; (b) pharmacological inhibition of P13 kinase and MAP kinase pathways abrogated the CxCLl2 induced invasion of PC-3 cells; (c) CxCLl2 induced Aktl phosphorylation and Aktl siRNA transfections abrogated the CxCLl2 induced Akt phosphorylation, proMMP-9 secretion, migration and invasion of PC-3 cells. This data suggests that chemoattractive mechanisms may involve migration of cancer cells towards bone tissue, and that cell signaling induced by binding of thechemokine to its receptor leads to the activation of multiple signaling pathways and subsequent release of MMPs into the local environment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA437261
Entities
People
- Sreenivasa R. Chinni
Organizations
- Wayne State University