SDF-1 alone and in co-operation with HGF regulates biology of human cervical carcinoma cells.
Stromal Derived Factor-1 (SDF-1)-CXCR4 axis plays a pivotal role in biology and metastasis of several tumors. The aim of this study was to see if SDF-1 alone or in combination with Hepatocyte Growth Factor (HGF) affects biology of human cervical carcinoma (HCC) cells. We found that HCC cell lines investigated in our study highly express CXCR4 on their surface. CXCR4 was also expressed on tumor cells in tissue sections derived from cervical cancer patients. At the same time normal cervical epithelium was negative for CXCR4 expression what suggests a strong correlation between CXCR4 and malignant cell phenotype. Subsequently, we studied a potential role of the SDF-1-CXCR4 axis in HCC and noticed that SDF-1 (i) chemoattracted HCC cells, (ii) enhanced their scattering, (iii) stimulated nuclear localization of beta-catenins and upregulated their target gene cyclin D1 and (iv) at the molecular level induced calcium flux and activated RAS-MAPK, PI3-AKT and JAK-STAT pathways. SDF-1-mediated functions were additionally enhanced in the presence of HGF. Thus, our data show that the SDF-1-CXCR4 axis affects biology of HCC cells. Furthermore, we postulate that this axis might become a potential target to prevent progression of cervical cancer.
Majka
Marcin
M
Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland. mmajka@cm-uj.krakow.pl
Drukala
Justyna
J
Lesko
Ewa
E
Wysoczynski
Marcin
M
Jenson
Alfred B
AB
Ratajczak
Mariusz Z
MZ
D000199:Actins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D006367:HeLa Cells; D017228:Hepatocyte Growth Factor / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics*; D021381:Protein Transport / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C066855:HGF protein, human; D019718:Receptors, CXCR4; D051176:beta Catenin; D017228:Hepatocyte Growth Factor