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Evaluation of CCR1 Antagonists on CCL3‐mediated receptor internalization
Author(s) -
Gilchrist Annette,
Cook Kayla
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.629.2
Subject(s) - ccr1 , chemokine receptor , internalization , chemokine , flow cytometry , ccl3 , cancer research , chemistry , multiple myeloma , bone marrow , microbiology and biotechnology , receptor , biology , immunology , biochemistry , ccl2
Multiple Myeloma (MM) is a cancer of plasma cells, the white blood cells that produce antibodies. MM is characterized by an accumulation of malignant plasma cells in the bone marrowand the presence of osteolytic lesions. CCR1 is a chemokine receptor expressed on a variety of cell types, including myeloma cells. While several chemokines can activate CCR1 only CCL3 has been consistently observed to be expressed and secreted in most MM cell cultures, primary MM bone marrow, and patient serum samples. Moreover, CCL3 has been shown to stimulate migration and proliferation of MM cells. We evaluated a collection of novel pyrrolidine compounds based on a previously disclosed series of CCR1 antagonists, and found that some compounds had stronger effects than others. We measured responses through the use of flow cytometry to measure surface expression of CCR1 and CCR5 on RPMI 8226 cells, a multiple myeloma cell line.