Anti-CXCR4 Monoclonal antibody, clone 3C22 [Biotin]

The signalling pathways involved in metastasis of oral adenoid cancer cells (TYS) in response to cancer-associated fibroblasts (COM D24) and normal oral mucosal fibroblasts (MM1) was examined. Metastatic cell behaviour was observed by cell-scatter, 3-D-collagen gel migration, and 3-D-spheroid invasion assays. Akt (v-Akt murine thymoma viral oncogene), MAPK(Mitogen activated protein kinase), EGFR (Epidermal growth factor receptor), TGF beta RI (Transforming growth factor beta receptor 1), and CXCR4 (C-X-C chemokine receptor 4) inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western blotting. COM-CM (conditioned medium from COM D24 cells) and MM1-CM (conditioned medium from MM1 cells) stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM-induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into collagen gels from the spheroids was stimulated by CM from both fibroblast cell lines, compared to the negative control. COM cells stimulated TYS invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive the addition of an EGFR inhibitor. This suggests that CAFs stimulate head and neck cancer cell migration and invasion in an Akt- dependent manner. Akt may represent a potential target for inhibitor design to treat metastatic head and neck cancer.

C-X-C motif chemokine receptor 4 (CXCR4) is expressed on the surface of various cell types involved in atherosclerosis, with a particularly rich receptor expression on macrophages and T cells. First pilot studies with Ga-68-pentixafor, a novel CXCR4-directed PET tracer, have shown promise to noninvasively image inflammation within atherosclerotic plaques. The aim of this retrospective study was to investigate the performance of Ga-68-pentixafor PET/CT for imaging atherosclerosis in comparison to F-18-FDG PET/CT. Methods: Ninety-two patients (37 women and 55 men; mean age, 62 +/- 10 y) underwent Ga-68-pentixafor and F-18-FDG PET/CT for staging of oncologic diseases. In these subjects, lesions in the walls of large arteries were identified using morphologic and PET criteria for atherosclerosis (n = 652). Tracer uptake was measured and adjusted for vascular lumen (background) signal by calculation of target-tobackground ratios (TBRs) by 2 investigators masked to the other PET scan. On a lesion-to-lesion and patient basis, the TBRs of both PET tracers were compared and additionally correlated to the degree of arterial calcification as quantified in CT. Results: On a lesion-tolesion basis, esGa-pentixafor and F-18-FDG uptake showed a weak correlation (r = 0.28; P < 0.01). Ga-68-pentixafor PET identified more lesions (n = 290; TBR 1.6, P < 0.01) and demonstrated higher uptake than F-18-FDG PET (1.8 0.5 vs. 1.4 0.4; P < 0.01). The degree of plaque calcification correlated negatively with both (68)G-apentixafor and F-18-FDG uptake (r =-0.38 vs.-0.31, both P < 0.00001). Conclusion: CXCR4-directed imaging of the arterial wall with Ga-68-pentixafor PET/CT identified more lesions than F-18-FDG PET/CT, with only a weak correlation between tracers. Further studies to elucidate the underlying biologic mechanisms and sources of CXCR4 positivity, and to investigate the clinical utility of chemokine receptor-directed imaging of atherosclerosis, are highly warranted.