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

Abstract

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.

High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients

“…CC chemokine receptor 7-positive cells were widely seen among the epithelial cancer cells (Figure 5A), and CCR7-positive cells were seen in the cancer stroma (Figure 5A). Dendritic cells and memory T cells express CCR7; these cells participate in acquired immune responses and antitumour effects (Croci et al , 2007). Therefore, CCR7-positive epithelial cancer cells and cells infiltrating the cancer stroma may join up to improve the overall survival rates in a postoperative patient with lung adenocarcinoma (Figures 2A and 5A).…”

G-protein coupled chemoattractant receptors and cancer

“…In addition to CXCR4, other chemokine GPCRs such as CXCR1 ( 16), CXCR2 (15,16,18,22), CXCR5 (7), CXCR6 (23), CXCR7 (23), CCR1 (41), CCR4 (81,82), CCR6 (23,(83)(84)(85)(86)(87)(88)(89)(90)(91), CCR7 (23,(92)(93)(94)(95)(96)(97)(98)(99)(100), CCR10 (23,26,101), CCR11 (102) and CX3CR1(103) are also implicated in mediating the metastasis of cancer cells (Table 1). Quantitative real-time RT-PCR revealed substantial expression of CCR7, CCR9 and CXCR6 as well as CXCR4 mRNA in nasopharyngeal carcinoma (NPC) cell lines (23).…”