Premium
Role of CXCR7 in breast cancer using molecular imaging techniques
Author(s) -
Foerster Bradley R.,
Luker Kathryn E.,
Luker Gary D
Publication year - 2007
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.21.6.a775-d
Subject(s) - transfection , green fluorescent protein , endosome , cancer cell , cancer research , in vivo , microbiology and biotechnology , chemistry , biology , cell culture , cancer , intracellular , gene , biochemistry , genetics
Purpose: To analyze the intracellular localization and function of CXCR7, a chemokine receptor commonly expressed in breast cancer. Methods: We engineered two separate expression constructs for CXCR7: a CXCR7‐GFP fusion protein for optical imaging of CXCR7 expression and localization; and unfused CXCR7 co‐expressed with GFP to identify transfected and transduced cells. We analyzed subcellular localization of CXCR7‐GFP in endosomes and lysosomes by co‐transfecting 293T cells with Rab5a, Rab7a, or Lamp1 fused to CFP. To establish cells that stably overexpress CXCR7, we transduced MDA‐MB‐231 breast cancer cells with a lentiviral vector for CXCR7‐GFP. These cells were used for wounding assays of cell migration in vitro and in vivo studies of tumor growth in Ncr nude mice. Results: In conditions of full serum, CXCR7 co‐localizes with Lamp1 (lysosomes) and also with Rab7 (late endosomes) but not with Rab5a (early endosomes). CXCR7 MDA‐MB‐231 cells showed significantly increased motogenesis compared to control cells. In vivo, growth of orthotopic tumor xenografts of CXCR7‐GFP transduced MDA‐MB‐231 cells was nearly three times greater than control cells expressing GFP alone. Conclusions: CXCR7 significantly increases the in vitro migration of breast cancer cells and the growth of human breast cancer cells in a mouse xenograft model. These data suggest that CXCR7 may be a key regulator of breast cancer biology. In vivo tumor volume over time of MDA‐231 cells transfected with CXCR7‐GFP vs. pSico (GFP only)