CXCR‐4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells

Hong, Jisoo; Pai, Hyun-Kyung; Hong, Kyoung‐Ok; Kim, Mi-Ae; Kim, Ji Eun; Lee, Jae‐Il; Hong, Sam-Pyo; Hong, Seong‐Doo

doi:10.1111/j.1600-0714.2008.00671.x

Cited by 25 publications

(22 citation statements)

References 19 publications

(30 reference statements)

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“…CXCR4 expression was significantly higher in OSCC cells (SCC15, CAL27, SCC25, UM1, and UM2) than in NOK cells siRNA [22]. Uchida et al used CXCR4 siRNA and subcutaneous injections of AMD3100 and found that cancer formation and lymph node metastasis were significantly inhibited [23,24]. In the line with these observations, our results showed that as a highly selective CXCR4 antagonist, AMD3100 could inhibit CXCL12 combining its receptor Fig.…”

Section: Discussionsupporting

confidence: 92%

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

et al. 2015

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The chemokine CXCL12 and its receptors CXCR4 and CXCR7 might play important roles in the occurrence and development of oral squamous cell carcinoma (OSCC). While CXCR4 expression is associated to initiation and progression of OSCC, the role of CXCR7, the recently founded second CXCL12 receptor, has not yet been elucidated in OSCC. In this study, CXCR4 and CXCR7 expressions were evaluated using western blot and quantitative RT-PCR in OSCC cells. AMD3100 (CXCR4 antagonist) was used to inhibit the activation of CXCR4. In contrast to CXCR4, effective CXCR7 small interfering RNA (siRNA) segments were used to silence CXCR7 in OSCC cells. The biological effects of CXCL12-CXCR4/CXCR7 axis on OSCC cell lines were studied by CCK-8 and transwell assay. As determined by RT-PCR and Western blot, CXCR7 expression was significantly downregulated after siRNA transfection in OSCC cells, and thus significantly promoted OSCC cell migration and invasion in vitro. The relative roles of the two CXCL12 receptors were further assessed by CXCR7 knockdown or deactivate CXCR4 receptor alone, or in combination, in the OSCC cells. In vitro functional analyses indicated that, in response to their common ligand (CXCL12), both receptors induced inhibition of proliferation and migration in OSCC cells in a dose-dependent manner. Exogenous CXCL12 could promote cell migration and invasion. In conclusion, our results indicated that CXCL12 which combined its receptor CXCR4 and CXCR7 together could promote cell motilities of OSCC.

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Section: Discussionsupporting

confidence: 92%

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

et al. 2015

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“…In addition, several reports have suggested that a decrease in CXCR4 expression inhibits CXCL12-induced migration of prostate cancer or lung cancer cells (30–32). The discovery of CXCR7 as a promiscuous receptor for CXCL11 and CXCL12 ended the previously accepted exclusive association between CXCL12 and CXCR4.…”

Section: Discussionmentioning

confidence: 99%

CXCR4, but not CXCR7, Discriminates Metastatic Behavior in Non–Small Cell Lung Cancer Cells

Choi

Burdick

Strieter

et al. 2014

Molecular Cancer Research

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Chemokines have been implicated as key contributors of non-small cell lung cancer (NSCLC) metastasis. However, the role of CXCR7, a recently discovered receptor for CXCL12 ligand, in the pathogenesis of NSCLC is unknown. To define the relative contribution of chemokine receptors to migration and metastasis we generated human lung A549 and H157 cell lines with stable knockdown of CXCR4, CXCR7, or both. Cancer cells exhibited chemotaxis to CXCL12 that was enhanced under hypoxic conditions, associated with a parallel induction of CXCR4, but not CXCR7. Interestingly, neither knockdown cell line differed in the rate of proliferation, apoptosis or cell adherence; however, in both cell lines, CXCL12-induced migration was abolished when CXCR4 signaling was abrogated. In contrast, inhibition of CXCR7 signaling did not alter cellular migration to CXCL12. In an in vivo heterotropic xenograft model using A549 cells, expression of CXCR4, but not CXCR7, on cancer cells was necessary for the development of metastases. In addition, cancer cells knocked-down for CXCR4 (or both CXCR4 and CXCR7) produced larger and more vascular tumors as compared to wild-type or CXCR7 knock-down tumors, an effect that was attributable to cancer cell-derived CXCR4 out competing endothelial cells for available CXCL12 in the tumor microenvironment. These results indicate that CXCR4, not CXCR7, expression engages CXCL12 to mediate NSCLC metastatic behavior.

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“…Among the mediators that explain this increase in CXCR4/CXCL12 mediated aggressiveness, ERK-1/2 [15,16,[21][22][23], Akt [16,22,23], Hsp90 [24,25], and NFkB [22] pathways have been cited. Furthermore, CXCR4/CXCL12 axis blockage implies a decrease in vitro invasiveness and migration [9,26], and a decrease in in vivo capacity for metastasis in experimental models [9,23]. The increase in invasiveness and metastasization related to CXCR4/CXCL12 expression has been linked to an increment in MMP-9 [17,21] and MMP-13 [15] activity.…”

Section: Discussionmentioning

confidence: 96%

Expression of the CXCL12/CXCR4 chemokine axis predicts regional control in head and neck squamous cell carcinoma

León

Diez

García

et al. 2016

Eur Arch Otorhinolaryngol

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Expression of the CXCL12/CXCR4 chemokine axis has been related with the appearance of metastatic recurrence survival, including regional and distant recurrence, in patients with head and neck squamous cell carcinoma (HNSCC). RT-PCR was used to determine mRNA expression levels of CXCL12 and CXCR4 in biopsy tumor samples in 111 patients with HNSCC. Five-year regional recurrence-free survival for patients with low CXCR4 expression (n = 39, 31.5 %) was 97.4 %, for patients with high CXCR4/high CXCL12 expression (n = 22, 19.8 %) it was 94.7 %, and for patients with high CXCR4/low CXCL12 expression (n = 50, 45.0 %) it was 63.3 %. We found significant differences in the regional recurrence-free survival according to CXCR4/CXCL12 expression values (P = 0.001). HNSCC patients with high CXCR4 and low CXCL12 expression values had a significantly higher risk of regional recurrence and could benefit from a more intense treatment of lymph node areas in the neck.

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CXCR‐4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells

Abstract: These results suggest that the downregulation of CXCR-4 induces anti-proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful target molecule for the treatment of OSCC.

Cited by 25 publications

References 19 publications

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

CXCR4, but not CXCR7, Discriminates Metastatic Behavior in Non–Small Cell Lung Cancer Cells

Expression of the CXCL12/CXCR4 chemokine axis predicts regional control in head and neck squamous cell carcinoma

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