The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells.
Cell migration is essential in many diverse processes ranging from embryonic development to wound healing and immune response. Cancer cells have recently been shown to utilize chemoattraction mechanisms mediated by chemokines and their respective receptors, e.g., the CXCL12/CXCR4 pathway normally found in leukocytes. Here we show that Slit2, a secreted protein signaling through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, acts as a potent chemoattractant for breast cancer cells. Comparing cell lines specifically metastasizing to either brain or bone, we found significant differences in their responses to CXCL12 and Slit2 treatments, suggesting a role for Slit/Robo signaling in brain metastasis.
Schmid
Bernd C
BC
Division of Gynecology, Molecular Oncology Group, Department of Obstetrics and Gynecology, Medical University of Vienna, Währinger Gürtel 18-20, EBO 05Q, 1090, Vienna, Austria.
Rezniczek
Günther A
GA
Fabjani
Gerhild
G
Yoneda
Toshiyuki
T
Leodolter
Sepp
S
Zeillinger
Robert
R
D001932:Brain Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000502:physiology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D054377:Chemokine CXCL12; D036341:Intercellular Signaling Peptides and Proteins; D020780:Matrix Metalloproteinase 9; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C515255:CXCL12 protein, human