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. 2016 Mar 15;114(6):697-703.
doi: 10.1038/bjc.2016.4. Epub 2016 Feb 18.

Ectopic expression of the chemokine CXCL17 in colon cancer cells

Lina Ohlsson  1 , Marie-Louise Hammarström  1 , Gudrun Lindmark  2 , Sten Hammarström  1 , Basel Sitohy  3
Affiliations

Ectopic expression of the chemokine CXCL17 in colon cancer cells

Lina Ohlsson et al. Br J Cancer. .

Abstract

Background: The novel chemokine CXCL17 acts as chemoattractant for monocytes, macrophages and dendritic cells. CXCL17 also has a role in angiogenesis of importance for tumour development.

Methods: Expression of CXCL17, CXCL10, CXCL9 and CCL2 was assessed in primary colon cancer tumours, colon carcinoma cell lines and normal colon tissue at mRNA and protein levels by real-time qRT-PCR, immunohistochemistry, two-colour immunofluorescence and immunomorphometry.

Results: CXCL17 mRNA was expressed at 8000 times higher levels in primary tumours than in normal colon (P < 0.0001). CXCL17 protein was seen in 17.2% of cells in tumours as compared with 0.07% in normal colon (P = 0.0002). CXCL10, CXCL9 and CCL2 mRNAs were elevated in tumours but did not reach the levels of CXCL17. CXCL17 and CCL2 mRNA levels were significantly correlated in tumours. Concordant with the mRNA results, CXCL10- and CXCL9-positive cells were detected in tumour tissue, but at significantly lower numbers than CXCL17. Two-colour immunofluorescence and single-colour staining of consecutive sections for CXCL17 and the epithelial cell markers carcinoembryonic antigen and BerEP4 demonstrated that colon carcinoma tumour cells indeed expressed CXCL17.

Conclusions: CXCL17 is ectopically expressed in primary colon cancer tumours. As CXCL17 enhances angiogenesis and attracts immune cells, its expression could be informative for prognosis in colon cancer patients.

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Figures

Figure 1
Figure 1
Relative mRNA levels of CXCL17, CXCL10, CXCL9 and CCL2 in primary colon cancer tissue (CC, stages I–IV; n=32) and normal colon retrieved from the proximal or distal resection margins (CTR; n=30). Relative quantity (RQ) was calculated as described in Materials and Methods section. Statistically significant differences are depicted, ***P<0.0001.
Figure 2
Figure 2
Correlation between mRNA levels of CXCL17 and CCL2 in primary colon cancer tissue (stages I–IV; n=32). Relative quantity (RQ) was calculated as described in Materials and Methods section.
Figure 3
Figure 3
Two-colour immunofluorescence staining of primary colon cancer tissue with anti-CXCL17 mAb and BerEP4. Two different tissue sections are shown. Section one (A, C, E) and section two (B, D, F). (A, B) Anti-CXCL17 mAb; red colour. (C, D) BerEP4 mAb; green colour. (E, F) Overlay; yellow colour of double-stained areas. Magnification: × 200. Section one shows many double-positive cells, whereas section two shows relatively few double-positive cells.
Figure 4
Figure 4
Immunoperoxidase staining of tissue sections of primary colon cancer tumour and normal colon with anti-CXCL17 mAb and anti-CEA mAb. (A) Anti-CXCL17 staining of primary tumour at low magnification, × 32. (B) Anti-CXCL17 staining of primary tumour at high magnification, × 200. The area enlarged is indicated in A. (C) Anti-CXCL17 staining of normal colon at low magnification, × 32. (D) Anti-CEA staining of primary tumour at low magnification, × 32. (E) Anti-CEA staining of primary tumour at high magnification, × 200. The area enlarged is indicated in D. (F) Conjugate control at high magnification, × 200. Note that A and D, and B, E and F are consecutive sections.
Figure 5
Figure 5
Immunoperoxidase staining of tissue sections of primary colon cancer tumour and normal colon with anti-CXCL10 mAb. (A) Anti-CXCL10 staining of primary tumour at low magnification, × 32. (B) Anti-CXCL10 staining of primary tumour at high magnification, × 200. The enlarged area is indicated in A. (C) Anti-CXCL10 staining of normal colon at low magnification, × 32.
Figure 6
Figure 6
Frequencies of CXCL17-, CXCL10- and CXCL9-positive cells in primary colon cancer tissue (CC) and normal colon tissue (CTR) as determined by immunomorphometry according to Weibel (1979). (A) Tumour cells compared with normal epithelial cells. (B) Tumour stroma compared with lamina propria in normal tissue. Ten primary tumours, stages I–IV and 9–10 normal colon samples were analysed. Bars represent mean+1s.e.m. P-values for comparison between tumour and normal tissue by two-sided Mann–Whitney t-test are given. ***P<0.001 and **P<0.01.
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