ELR+ CXC chemokine expression in benign and malignant colorectal conditions.
BACKGROUND
CXCR2 chemokine ligands CXCL1, CXCL5 and CXCL6 were shown to be involved in chemoattraction, inflammatory responses, tumor growth and angiogenesis. Here, we comparatively analyzed their expression profile in resection specimens from patients with colorectal adenoma (CRA) (n = 30) as well as colorectal carcinoma (CRC) (n = 48) and corresponding colorectal liver metastases (CRLM) (n = 16).


METHODS
Chemokine expression was assessed by microdissection, quantitative real-time PCR (Q-RT-PCR), the enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC).


RESULTS
In contrast to CXCL6, we demonstrated CXCL1 and CXCL5 mRNA and protein expression to be significantly up-regulated in CRC and CRLM tissue specimens in relation to their matched tumor neighbor tissues. Moreover, both chemokine ligands were demonstrated to be significantly higher expressed in CRC tissues than in CRA tissues thus indicating a progressive increase in the transition from the premalignant condition to the development of the malignant status. Although a comparative analysis of the CXCL1/CXCL5 protein expression profiles in CRC patients revealed that the absolute expression level of CXCL1 was significantly higher in comparison to CXCL5, mRNA- and protein overexpression of CXCL5 in CRC and CRLM tissues was much more pronounced (80- and 60- fold in CRC tissues, respectively) in comparison to CXCL1 (5- and 3.5- fold in CRC tissues, respectively).


CONCLUSIONS
Our results demonstrate a significant association between CXCL1 and CXCL5 expression with CRC and CRLM suggesting for both chemokine ligands a potential role in the progression from CRA to CRC and thus, in the initiation of CRC.
Rubie
Claudia
C
Dept. of General -, Visceral-, Vascular - and Pediatric Surgery, University of the Saarland, 66421 Homburg/Saar, Germany. ca.labor@uks.eu
Frick
Vilma Oliveira
VO
Wagner
Mathias
M
Schuld
Jochen
J
Gräber
Stefan
S
Brittner
Brigitte
B
Bohle
Rainer M
RM
Schilling
Martin K
MK
D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054360:Chemokine CXCL1 / Q000096:biosynthesis / Q000235:genetics; D054365:Chemokine CXCL5 / Q000096:biosynthesis / Q000235:genetics; D054427:Chemokine CXCL6 / Q000096:biosynthesis / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; C515503:CXCL6 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D012333:RNA, Messenger