title: Inhibition of CXCR4 by CTCE-9908 inhibits breast cancer metastasis to lung and bone.
abstract: Metastasis occurs, in part, due to tumor cell responses to chemokine secretion by ectopic organs or tissues. SDF-1 is constitutively expressed in tissues where metastases frequently develop while breast carcinoma cells express the receptor for SDF-1, CXCR4, which is correlated with increased bone metastasis and poor overall survival. We hypothesized that treatment with a CXCR4 antagonist, CTCE-9908, would decrease incidence of bone and lung metastasis. Treatment with CTCE-9908 (25 mg/kg) began the day prior to or the day of intravenous or intracardiac tumor cell inoculation of MDA-MB-231 human breast carcinoma cells expressing enhanced green fluorescent protein (GFP) into athymic mice. After 5 or 8 weeks (i.c. and i.v. injections, respectively), the presence of fluorescent foci at metastatic sites was assessed. Somewhat surprisingly, CTCE-9908 treatment did not decrease incidence of metastasis as hypothesized. However, CTCE-9908 did decrease metastatic burden (i.e., size of metastases) in all organs examined (lungs, bone, heart, liver, kidneys, pancreas and spleen). Based upon this and other studies, the use of CTCE-9908 is promising as an adjuvant therapy for metastatic disease.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Richert
authors.forename: Kedar S
authors.initials: KS
authors.lastname: Vaidya
authors.forename: Caroline N
authors.initials: CN
authors.lastname: Mills
authors.forename: Donald
authors.initials: D
authors.lastname: Wong
authors.forename: Walter
authors.initials: W
authors.lastname: Korz
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Hurst
authors.forename: Danny R
authors.initials: DR
authors.lastname: Welch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000627:therapeutic use*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C540323:CTCE-9908; C527276:CXCR4 protein, human; D010455:Peptides; D019718:Receptors, CXCR4