Overexpression of CXCR7 accelerates tumor growth and metastasis of lung cancer cells

Abstract

Background Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in more than 20 human malignancies, among which lung cancer is the leading cause of cancer-associated deaths worldwide. Thus, the mechanism of CXCR7 in the progression of lung cancer is urgently needed. Methods First, we explored CXCR4 and CXCR7 expression in human lung cancer specimens and cell lines by immunohistochemistry, western blot and flow cytometry. Then, we chose the human lung adenocarcinoma cell line A549 that stably overexpressed CXCR7 through the way of lentivirus-mediated transduction. Next, “wound healing” assay and transwell assay were applied to compare the cell migration and invasion ability, and stripe assay was used to evaluate the cell polarization. Last, our team established a mouse xenograft model of human lung cancer and monitored tumor proliferation and metastasis by firefly luciferase bioluminescence imaging in SCID/Beige mice. Results In clinical lung cancer samples, CXCR7 expression was almost not detected in normal tissue but upregulated in lung tumor tissue, whereas, CXCR4 was highly expressed in both normal and tumor tissues. Furthermore, overexpression of CXCR7 enhanced A549 cell migration and polarization in vitro. Besides, mouse xenograft model of human lung cancer showed that CXCR7 promoted primary lung tumor’s growth and metastasis to the second organ, such as liver or bone marrow in SCID/Beige mice in vivo. Conclusions This study describes the multiple functions of CXCR7 in lung cancer. Thus, these results suggest that CXCR7 may be a malignancy marker and may provide a novel target for anticancer therapy.

The CXCL12/CXCR4/ACKR3 Signaling Axis Regulates PKM2 and Glycolysis

“…CXCL12 likely promotes glycolytic metabolism through other processes activated by CXCL12 signaling through CXCR4 and/or ACKR3, including ERK and Akt. Collectively, these, and potentially other CXCL12-dependent pathways, support the increased proliferation of cancer cells previously reported by our group and others [ 12 , 13 , 48 , 49 , 50 ].…”

WITHDRAWN: Stromal Cell-Derived Factor 1 Secreted by Cancer- Associated Fibroblasts Promotes lncRNA Xist through CXCR4 and Facilitates Invasion and Metastasis of Non-Small Cell Lung Cancer

“…SDF-1, also known as Chemokine 12 (CXCL12) is ubiquitously expressed in many tissues and cell types, and it can speci cally interact with the ligand for CXCR4 [16]. In clinical LC samples, CXCR4 is highly expressed in both normal and tumor tissues [17]. The CXCL12/SDF-1 and its receptor CXCR4 play a major role in tumor initiation, promotion, progression and metastasis [12,13,18].…”

Circulating hsa_circ_0072309, acting via the miR‐100/ACKR3 pathway, maybe a potential biomarker for the diagnosis, prognosis, and treatment of brain metastasis from non‐small‐cell lung cancer

“…Earlier studies have revealed that hsa_circ_0072309 is significantly overexpressed in human NSCLC tissues when compared to matching normal samples and elevated in A549 LC cells when compared to BEAS‐2B normal lung cells, where it promotes NSCLC cell proliferation, migration, and invasion while inhibits apoptosis 42,43 . Similarly, CXCR7 (ACKR3) is overexpressed in lung tumor tissues, and upregulation of CXCR7 markedly promotes A549 cell migration in vitro and enhances tumor growth and metastasis in vivo 44,45 . In contrast, miR‐100 is substantially downregulated in NSCLC tissues, and miR‐100 restoration can inhibit the formation of tumors, the advancement of the G2/M cell cycle, and the proliferation, invasion, and migration of NSCLC cells 20,46,47 .…”