Limits...
CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases.

Mir H, Singh R, Kloecker GH, Lillard JW, Singh S - Oncotarget (2015)

Bottom Line: High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined.Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls.Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.

ABSTRACT
Lung cancer (LuCa) is the leading cause of cancer-related deaths worldwide regardless of the gender. High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined. Here, we present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of LuCa. CXCR6 expression was significantly higher in two subtypes of NSCLC (adenocarcinomas-ACs and squamous cell carcinoma-SCCs) as compared to non-neoplastic tissue. Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls. Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients. Biological significance of this axis was validated using SCC and AC cell lines. Expression of CXCR6 was higher in AC cells, which also showed higher migratory and invasive potential than SCC. Differences in migratory and invasive potential between AC and SCC were due to differential expression of metalloproteinases following CXCL16 stimulation. Hence, our findings suggest clinical and biological significance of CXCR6/CXCL16 axis in LuCa, which could be used as potential prognostic marker and therapeutic target.

No MeSH data available.


Related in: MedlinePlus

CXCR6 expression in tissues samples from LuCa patients(A) Representative images for CXCR6 tissue expression in lung tissues from non-neoplastic (n = 8), adenocarcinoma (n = 54) and squamous cell carcinoma (n = 24) were stained with isotype control or anti-CXCR6 antibodies. Brown (DAB) color shows CXCR6 staining. Images were captured using tissuefaxs cell analysis system from Tissuegnostics. (B) Immuno-intensities of CXCR6 were quantified using image analysis Aperio ImageScope v.6.25 software using ImageScope algorithm. ***p ≤ 0.0001 when compared between groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496412&req=5

Figure 1: CXCR6 expression in tissues samples from LuCa patients(A) Representative images for CXCR6 tissue expression in lung tissues from non-neoplastic (n = 8), adenocarcinoma (n = 54) and squamous cell carcinoma (n = 24) were stained with isotype control or anti-CXCR6 antibodies. Brown (DAB) color shows CXCR6 staining. Images were captured using tissuefaxs cell analysis system from Tissuegnostics. (B) Immuno-intensities of CXCR6 were quantified using image analysis Aperio ImageScope v.6.25 software using ImageScope algorithm. ***p ≤ 0.0001 when compared between groups.

Mentions: Tissue microarray consisting of lung tissues from healthy individuals (non-neoplastic; n = 8) and LuCa patients (AC; n = 54 and SCC; n = 24) was stained for CXCR6 and corresponding immuno-intensity was analyzed. Significantly higher CXCR6 expression was found in NSCLC (AC and SCC) as compared to non-neoplastic tissues (Figure 1A and 1B). Expression of CXCR6 was significantly (p ≤ 0.0001) higher in AC compared to SCC. Furthermore, there was a notable difference in the CXCR6 distribution pattern between AC and SCC. Expression of CXCR6 in SCC was predominantly nuclear. However in AC, CXCR6 was largely present in cell cytoplasm and membranes, in addition to nucleus. Serum analysis revealed elevated CXCL16 levels in LuCa patients as compared to healthy individuals (Figure 2). Serum CXCL16 was significantly higher in AC (p ≤ 0.0001) followed by SCC compared to healthy donors (p ≤ 0.0001). These results suggest clinical significance of CXCR6 and CXCL16 in LuCa.


CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases.

Mir H, Singh R, Kloecker GH, Lillard JW, Singh S - Oncotarget (2015)

CXCR6 expression in tissues samples from LuCa patients(A) Representative images for CXCR6 tissue expression in lung tissues from non-neoplastic (n = 8), adenocarcinoma (n = 54) and squamous cell carcinoma (n = 24) were stained with isotype control or anti-CXCR6 antibodies. Brown (DAB) color shows CXCR6 staining. Images were captured using tissuefaxs cell analysis system from Tissuegnostics. (B) Immuno-intensities of CXCR6 were quantified using image analysis Aperio ImageScope v.6.25 software using ImageScope algorithm. ***p ≤ 0.0001 when compared between groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496412&req=5

Figure 1: CXCR6 expression in tissues samples from LuCa patients(A) Representative images for CXCR6 tissue expression in lung tissues from non-neoplastic (n = 8), adenocarcinoma (n = 54) and squamous cell carcinoma (n = 24) were stained with isotype control or anti-CXCR6 antibodies. Brown (DAB) color shows CXCR6 staining. Images were captured using tissuefaxs cell analysis system from Tissuegnostics. (B) Immuno-intensities of CXCR6 were quantified using image analysis Aperio ImageScope v.6.25 software using ImageScope algorithm. ***p ≤ 0.0001 when compared between groups.
Mentions: Tissue microarray consisting of lung tissues from healthy individuals (non-neoplastic; n = 8) and LuCa patients (AC; n = 54 and SCC; n = 24) was stained for CXCR6 and corresponding immuno-intensity was analyzed. Significantly higher CXCR6 expression was found in NSCLC (AC and SCC) as compared to non-neoplastic tissues (Figure 1A and 1B). Expression of CXCR6 was significantly (p ≤ 0.0001) higher in AC compared to SCC. Furthermore, there was a notable difference in the CXCR6 distribution pattern between AC and SCC. Expression of CXCR6 in SCC was predominantly nuclear. However in AC, CXCR6 was largely present in cell cytoplasm and membranes, in addition to nucleus. Serum analysis revealed elevated CXCL16 levels in LuCa patients as compared to healthy individuals (Figure 2). Serum CXCL16 was significantly higher in AC (p ≤ 0.0001) followed by SCC compared to healthy donors (p ≤ 0.0001). These results suggest clinical significance of CXCR6 and CXCL16 in LuCa.

Bottom Line: High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined.Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls.Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.

ABSTRACT
Lung cancer (LuCa) is the leading cause of cancer-related deaths worldwide regardless of the gender. High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined. Here, we present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of LuCa. CXCR6 expression was significantly higher in two subtypes of NSCLC (adenocarcinomas-ACs and squamous cell carcinoma-SCCs) as compared to non-neoplastic tissue. Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls. Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients. Biological significance of this axis was validated using SCC and AC cell lines. Expression of CXCR6 was higher in AC cells, which also showed higher migratory and invasive potential than SCC. Differences in migratory and invasive potential between AC and SCC were due to differential expression of metalloproteinases following CXCL16 stimulation. Hence, our findings suggest clinical and biological significance of CXCR6/CXCL16 axis in LuCa, which could be used as potential prognostic marker and therapeutic target.

No MeSH data available.


Related in: MedlinePlus