Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer

AIM: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM). METHODS: IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6) colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16). RESULTS: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues. Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found. CONCLUSION: Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases.

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases

AIM:To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage Ⅳ colorectal cancer(CRC) patients.METHODS:Using Real Time-PCR,enzyme-linked immunosorbent assay,Western Blots and immunohistochemistry,we have analyzed the expression of CCL20,CCR6 and proliferation marker Ki-67 in colorectal liver metastasis(CRLM) specimens from stage Ⅳ CRC patients who received preoperative FOLFOX chemotherapy(n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery(n = 29).RESULTS:Of the 53 patients who received FOLFOX,time to liver surgery was ≤ 1 mo in 14 patients,≤ 1 year in 22 patients and > 1 year in 17 patients,respectively.In addition,we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups.Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery(P < 0.001) in comparison to patients who did not undergo FOLFOX treatment.Further,proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment.CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy.CONCLUSION:This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.