Rabbit Anti-Human CSF1 monoclonal antibody, clone TV0524

Intratumoral hypoxia induces the recruitment of stromal cells, such as macrophages and mesenchymal stem cells (MSCs), which stimulate invasion and metastasis by breast cancer cells (BCCs). Production of macrophage colony-stimulating factor 1 (CSF1) by BCCs is required for macrophage recruitment, but the mechanisms underlying CSF1 expression have not been delineated. Triple-negative breast cancers have increased expression of genes regulated by hypoxia-inducible factors (HIFs). In this study, we delineate two feed-forward signaling loops between human MDA-MB-231 triple-negative BCCs and human MSCs that drive stromal cell recruitment to primary breast tumors. The first loop, in which BCCs secrete chemokine (C-X-C motif) ligand 16 (CXCL16) that binds to C-X-C chemokine receptor type 6 (CXCR6) on MSCs and MSCs secrete chemokine CXCL10 that binds to receptor CXCR3 on BCCs, drives recruitment of MSCs. The second loop, in which MSCs secrete chemokine (C-C motif) ligand 5 that binds to C-C chemokine receptor type 5 on BCCs and BCCs secrete cytokine CSF1 that binds to the CSF1 receptor on MSCs, drives recruitment of tumor-associated macrophages and myeloid-derived suppressor cells. These two signaling loops operate independent of each other, but both are dependent on the transcriptional activity of HIFs, with hypoxia serving as a pathophysiological signal that synergizes with chemokine signals from MSCs to trigger CSF1 gene transcription in triple-negative BCCs.

We describe the preliminary evaluation of the frequency corrections and their uncertainty in the cesium fountain primary frequency standard (PFS) NMIJ-F2 under development at National Metrology Institute of Japan (NMIJ). In NMIJ-F2, cold atoms generated from a vapor-loaded optical molasses in the (001) configuration are optically pumped to the Zeeman sublevels of m(F) = 0 to increase the number of atoms involved in the Ramsey interrogation. Moreover, a cryocooled sapphire oscillator with ultralow phase noise is employed as the local oscillator to avoid degradation of the frequency stability due to the Dick effect. As a result, we have obtained a very high fractional frequency stability of 9.7 x 10(-14 tau 1/2). As for systematic frequency shifts, the fractional correction for the second-order Zeeman shift is experimentally estimated to be (-165.5 +/- 0.5) x 10(-15) from the first-order Zeeman shift of atoms in m(F) = +1 launched to various heights. The fractional frequency correction for cold-atom collisions is estimated to be (+3.3 +/- 0.4) x 10(-15) by extrapolating the frequency to zero density from the frequencies measured for various nonzero atom numbers. We will soon be able to make a comparison with other atomic fountain PFSs at the 1 x 10(-15) level.