Study on CXCR4/SDF-1alpha axis in lymph node metastasis of cervical squamous cell carcinoma.
CXCR4/stromal-cell-derived factor-1alpha (SDF-1alpha) is involved in many cancer metastatic mechanisms. Cervical squamous cell cancer (SCC) tissues (n=35), normal cervical tissues (n=10), metastatic (n=10) and nonmetastatic lymph nodes (n=50), and Hela cells were stained immunohistochemically with CXCR4 monoclonal antibody (mAb). Meanwhile, lymph nodes were stained immunohistochemically with rabbit anti-SDF-1alpha. In vitro invasion of Hela cells was evaluated using Transwell Permeable Supports (Corning, NY), in which Hela cells with/without CXCR4 mAb preincubation were seeded in the upper chambers and medium containing 0-100 ng/mL SDF-1alpha was added to the lower compartments. For evaluating the effect of CXCR4/SDF-1alpha on proliferation of cervical cancer cells, Hela cells were cultured for 72 h exposed to SDF-1alpha with and without CXCR4 mAb. We found that CXCR4 was expressed on SCC cells in all cervical cancer, metastatic lymph node, and Hela cells but not in normal cervix. SDF-1alpha was expressed on lymph cells in all lymph nodes. SDF-1alpha induced the directed migration of Hela cells with a concentration-dependent model, which was inhibited by CXCR4 mAb (P<0.05). SDF-1alpha also stimulated the proliferation of Hela cells mediated by CXCR4 (P<0.05). CXCR4/SDF-1alpha axis probably participates in the metastasis toward lymph nodes in cervical cancer.
Zhang
J-P
JP
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Lu
W-G
WG
Ye
F
F
Chen
H-Z
HZ
Zhou
C-Y
CY
Xie
X
X
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4