Expression of a functional CCR7 chemokine receptor inhibits the post-intravasation steps of metastasis in malignant murine mammary cancer cells

Abstract

To study the role of the chemokine receptor CCR7 in the metastatic process, a murine CCR7 gene was transduced in two mammary cancer cell lines with different origins and molecular features; TS/A, derived from a spontaneous mammary cancer of BALB/c strain, and N202.1A, derived from a HER-2/neu transgenic mammary cancer (FVB background) and characterized by a high expression of HER-2/neu. Transduced CCR7 conferred to mammary cancer cells a chemotactic response towards CCL21 (a CCR7 ligand), but did not consistently affect in vitro growth properties. In vivo, CCR7-engineered cells gave rise to tumors in syngeneic hosts with growth rates similar to or slightly lower than the controls and with similar patterns of spontaneous metastases. When injected directly intravenously to study the late post-intravasation phases of metastasis, CCR7-engineered cells showed a strongly decreased lung colonizing ability. Such an effect was observed both with HER-2/neu-positive and -negative mammary cancer cells. When used as a prophylactic vaccine, CCR7-transduced cell vaccine succeeded in the long-term control of mammary tumorigenesis in 25% of the HER-2/neu transgenic females, suggesting an increased immunogenicity of CCR7-engineered cells.