CXCR4 and CXCR7 regulate angiogenesis and CT26.WT tumor growth independent from SDF‐1

Abstract

Recent studies have shown that the chemokine stromal cell-derived factor (SDF)-1 and its receptor CXCR4 are involved in the metastatic process of colorectal cancer. The impact of SDF-1 on the stimulated metastatic growth during hepatectomy-associated liver regeneration is unknown. With the use of a heterotopic murine colon cancer model, we analyzed whether blockade of SDF-1 inhibits angiogenesis and extrahepatic growth of colorectal cancer after liver resection. Functional neutralization of SDF-1 by 1 mg/kg body weight anti-SDF-1 antibody only slightly delayed the initial tumor cell engraftment but also did not reduce the size of established extrahepatic tumors compared with controls. Tumor cell apoptosis was increased by anti-SDF-1 treatment only during the early 5-9-day period of tumor cell engraftment, but was found significantly decreased during the late phase of tumor growth. The initial delay of tumor cell engraftment was associated with an increase of tumor capillary density and microvascular permeability. This was associated with an increased vascular endothelial growth factor (VEGF) expression and an enhanced tumor cell invasion of the neighboring tissue. In contrast to the neutralization of SDF-1, blockade of the SDF-1 receptors CXCR4 and CXCR7 significantly reduced tumor capillary density and tumor growth. Thus, our study indicates that neutralization of SDF-1 after hepatectomy is not capable of inhibiting angiogenesis and growth of extrahepatic colorectal tumors, because it is counteracted by the compensatory actions through an alternative VEGF-dependent pathway.

Llama-derived Single Variable Domains (Nanobodies) Directed against Chemokine Receptor CXCR7 Reduce Head and Neck Cancer Cell Growth in Vivo

“…CXCR7 can be therapeutically targeted by non-peptidergic small molecules, siRNA as well as conventional antibodies (3,11,18). In the present study we identified a novel class of potential therapeutics targeting CXCR7, llama-derived immunoglobulin single variable domains (Nanobodies) specifically directed against CXCR7.…”

CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment

“…12 The majority of the reports drew the conclusion that CXCR7 serves as a positive regulator in enhancing proliferation/metastasis of tumors. [13][14][15][16] Similar to CXCR4, the function of CXCR7 in tumor cells is still controversial. It was revealed by Liberman et al 17 and Uto-Konomi et al 18 that CXCR7 acted as a negative regulator for CXCL12/ CXCR4 axis and elicited anti-tumorigenic effects.…”

The Disparate Twins: A Comparative Study of CXCR4 and CXCR7 in SDF-1α–Induced Gene Expression, Invasion and Chemosensitivity of Colon Cancer

“…In humans, CXCR7 is expressed in embryonic and adult tissue as well as on tumor cells (10,12,13). Elevated levels of CXCR7 were observed in aggressive colon (14) and colorectal cancer brain metastases (15).…”