Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4.
Metastasis shares many similarities with leukocyte trafficking. Among those chemokine receptors thought to be involved in hemopoietic cell homing, stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4 (CXCR4) have received considerable attention. Like hemopoietic cell homing, levels of stromal cell-derived factor-1 are high at sites of breast cancer metastasis including lymph node, lung, liver, and the marrow. Moreover, CXCR4 expression is low in normal breast tissues and high in malignant tumors, suggesting that a blockade of CXCR4 might limit tumor metastasis. We therefore investigated the role of a synthetic antagonist 14-mer peptide (TN14003) in inhibiting metastasis in an animal model. Not only was TN14003 effective in limiting metastasis of breast cancer by inhibiting migration, but it may also prove useful as a diagnostic tool to identify CXCR4 receptor-positive tumor cells in culture and tumors in paraffin-embedded clinical samples.
Liang
Zhongxing
Z
Department of Hematology/Oncology, Winship Cancer Institute, Atlanta, Georgia 30322, USA.
Wu
Tao
T
Lou
Hong
H
Yu
Xiwen
X
Taichman
Russell S
RS
Lau
Stephen K
SK
Nie
Shuming
S
Umbreit
Jay
J
Shim
Hyunsuk
H
D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D010455:Peptides / Q000494:pharmacology* / Q000633:toxicity; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity; D023041:Xenograft Model Antitumor Assays
D010455:Peptides; D019718:Receptors, CXCR4; C488289:TN14003