The chemokine receptors <scp>CXCR</scp>1 and <scp>CXCR</scp>2 regulate oral cancer cell behaviour

Syed A. Khurram; Lynne Bingle; Brenka M. Mccabe; Paula M. Farthing; Simon A. Whawell

doi:10.1111/jop.12191

The chemokine receptors <scp>CXCR</scp>1 and <scp>CXCR</scp>2 regulate oral cancer cell behaviour

Syed A. Khurram^*, Lynne Bingle, Brenka M. Mccabe, Paula M. Farthing, Simon A. Whawell

^*Corresponding author for this work

Peninsula Dental School

University of Sheffield

Research output: Contribution to journal › Article › peer-review

Abstract

BackgroundChemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin‐8 (IL‐8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL‐8 and growth‐related oncogene‐α (which selectively binds CXCR2).MethodsmRNA and protein expression was studied using RT‐PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS‐based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays.ResultsmRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL‐8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL‐8) and CXCR2 (for GROα) as receptor‐blocking antibodies significantly inhibited the responses. IL‐8 and GROα also increased MMP‐9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP‐7 production was only seen in OCCL.ConclusionsFunctional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.

Original language	English
Pages (from-to)	667-674
Number of pages	0
Journal	Journal of Oral Pathology & Medicine
Volume	43
Issue number	9
Early online date	26 Jun 2014
DOIs	https://doi.org/10.1111/jop.12191
Publication status	Published - Oct 2014

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title = "The chemokine receptors CXCR1 and CXCR2 regulate oral cancer cell behaviour",

abstract = "BackgroundChemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin‐8 (IL‐8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL‐8 and growth‐related oncogene‐α (which selectively binds CXCR2).MethodsmRNA and protein expression was studied using RT‐PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS‐based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays.ResultsmRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL‐8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL‐8) and CXCR2 (for GROα) as receptor‐blocking antibodies significantly inhibited the responses. IL‐8 and GROα also increased MMP‐9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP‐7 production was only seen in OCCL.ConclusionsFunctional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.",

author = "Khurram, {Syed A.} and Lynne Bingle and Mccabe, {Brenka M.} and Farthing, {Paula M.} and Whawell, {Simon A.}",

year = "2014",

month = oct,

doi = "10.1111/jop.12191",

language = "English",

volume = "43",

pages = "667--674",

journal = "Journal of Oral Pathology & Medicine",

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T1 - The chemokine receptors CXCR1 and CXCR2 regulate oral cancer cell behaviour

AU - Khurram, Syed A.

AU - Bingle, Lynne

AU - Mccabe, Brenka M.

AU - Farthing, Paula M.

AU - Whawell, Simon A.

PY - 2014/10

Y1 - 2014/10

N2 - BackgroundChemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin‐8 (IL‐8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL‐8 and growth‐related oncogene‐α (which selectively binds CXCR2).MethodsmRNA and protein expression was studied using RT‐PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS‐based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays.ResultsmRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL‐8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL‐8) and CXCR2 (for GROα) as receptor‐blocking antibodies significantly inhibited the responses. IL‐8 and GROα also increased MMP‐9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP‐7 production was only seen in OCCL.ConclusionsFunctional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.

AB - BackgroundChemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin‐8 (IL‐8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL‐8 and growth‐related oncogene‐α (which selectively binds CXCR2).MethodsmRNA and protein expression was studied using RT‐PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS‐based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays.ResultsmRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL‐8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL‐8) and CXCR2 (for GROα) as receptor‐blocking antibodies significantly inhibited the responses. IL‐8 and GROα also increased MMP‐9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP‐7 production was only seen in OCCL.ConclusionsFunctional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.

U2 - 10.1111/jop.12191

DO - 10.1111/jop.12191

M3 - Article

SN - 0904-2512

VL - 43

SP - 667

EP - 674

JO - Journal of Oral Pathology & Medicine

JF - Journal of Oral Pathology & Medicine

IS - 9

ER -

The chemokine receptors <scp>CXCR</scp>1 and <scp>CXCR</scp>2 regulate oral cancer cell behaviour

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