Hypoxia-Induced Chemokine Activation And Lymphnode Metastases In Primary Cervix Xenografts

Aim: To examine the role of the chemokine pathway in cervix cancer in the regulation of hypoxia-induced metastases and bone marrow derived myeloid cells (BMDCs) in the tumor microenvironment. Methods: Cervix cancer biopsies from patients in clinical studies at PMH were used for implantation into the cervix of NRG mice. Relative CXCR4 expression by qRT-PCR in biopsies from 117 patients with cervical cancer and 17 primary, orthotopic, cervical cancer xenografts was conducted. Mice bearing orthotopic xenografts were exposed to cyclic hypoxia (12x 10min cycles of breathing 7%O2 or air; 4hr/day for 2 wks) during their growth in combination with AMD3100 (Plerixafor), administered by osmotic pumps (5mg/kg/day) implanted subcutaneously for 3 weeks. Primary tumor size and para-aortic lymph node metastases were assessedfor metastases (HE 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B13. doi:10.1158/1538-7445.CHTME14-B13