Changes in CXCL12/CXCR4-chemokine expression during onset of colorectal malignancies

Frick, Vilma Oliveira; Rubie, Claudia; Ghadjar, Pirus; Faust, Sabrina K.; Wagner, Mathias; Gräber, Stefan; Schilling, Martin K.

doi:10.1007/s13277-010-0112-y

Cited by 16 publications

(11 citation statements)

References 29 publications

(37 reference statements)

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“…Subsequently, we observed significant up-regulation of CXCR4 and significant down-regulation of CXCL12 in CRC tissues. This inverse expression pattern is supported by previous studies, where CXCR4 was shown to be highly up-regulated in all T-stages of CRC tissues [16] and CXCL12 expression levels were shown to be low at the base of the crypts and increased in the more differentiated apical intestinal epithelial cells [29,30]. In compliance with the low CXCL12 expression status in tissues we observed low or no CXCL12 expression, respectively, in three human CRC derived cell lines, non-metastatic cell line Caco-2 and metastatic cell lines SW480 and HT-29.…”

Section: Discussionsupporting

confidence: 80%

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

et al. 2011

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BackgroundInteractions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition.MethodsExpression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies.ResultsIn CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05).ConclusionsCXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions.

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Section: Discussionsupporting

confidence: 80%

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

et al. 2011

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“…Since the cytokines play an essential role in the communication between tumor cell initiation/progression and host anti-tumor immunity (6)(7)(8)(9)(10)(11), it is important to investigate the cytokine changes in the tumor microenvironment, in order to better understand the transitional mechanisms and design novel interventional strategies. Indeed, in previous studies, we and others have revealed that the colorectal neoplastic transformation leads to a remarkable alteration of cytokine secretion in the tumor immune microenvironment (6,8,12,13), this may have a significant role in predicting the progression from the adenomas to CRCs (12,14,15) and prognosis of the CRCs (7,9,10,12,13,16).…”

Section: Introductionmentioning

confidence: 86%

Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

Cui

Gundersen

et al. 2014

Cancer Immunol Immunother

108

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Most sporadic colorectal cancers (CRCs) develop from preexisting adenomas. The transition from an adenoma to a CRC leads to disruption in cytokine secretion and immune imbalance.Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family, and involved in the regulation of immune function and development of chronic colorectal inflammation and cancers. However, the activation of the IL33/ST2 axis alongside the colorectal adenoma-carcinoma sequence is poorly understood. Our aim is to evaluate the dynamics between the IL-33/ST2 axis and the human colorectal normaladenoma -carcinoma sequence. The expression of IL-33 in adenomas (n=50) determined by real-time PCR was significantly higher than that in the colorectal mucosa from normal individuals. The expression of IL-33 was also increased in CRCs (n=50) when compared to the normal control group. Significantly lower levels of IL-33 where found in the CRCs compared with the adenomas; moreover, the analysis revealed that a high IL-33 level was associated with a low dysplasia degree in the adenomas, as well as with a statistically nonsignificant increase of survival time in the CRC patients. The increased expression of IL-33 in adenomas/CRCs was confirmed by immunohistochemistry (IHC) which showed that IL-33 immunoreactivity was expressed in the adenomatous/cancerous epithelium, whereas it was undetectable in the normal controls. IHC also confirmed that the IL-33 receptor (ST2) is increased in tumor stromal cells. Double IHCs identified that IL-33 immunoreactivity was in the tumor stromal myofibroblasts and microvessels. In conclusion, the expression of IL-33 in the tumor microenvironment was dynamically altered along the colorectal adenomacarcinoma sequence; and may be a potential predictor for the progression of the adenoma to the CRC.3

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“…Furthermore, recent results of our previous studies indicated that a correlation existed between CXCR4 expression and colorectal liver metastasis development (32). CXCR4 mRNA silencing was also shown to abrogate the CXCL12-induced migration of colorectal cancer cells (33).…”

Section: Discussionmentioning

confidence: 81%

CXCL12/CXCR4 display an inverse mRNA expression profile in gastric carcinoma that correlates with tumor progression

et al. 2015

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Abstract. Chemokines and their receptors have been shown to contribute to tumor growth and metastatic spread in various gastrointestinal cancer entities. In the present study, the mRNA expression profiles and clinical significance of chemokine ligand CXCL12 and its corresponding receptor CXCR4 were investigated in patients with gastric cancer (GC). Using quantitative polymerase chain reaction, the expression profile of CXCL12/CXCR4 was analyzed in resection specimens from the patients with GC (n=66) and in corresponding normal gastric tissues. Upon investigating CXCL12/CXCR4 mRNA expression levels in the GC tissues, significant downregulation of CXCL12 expression was demonstrated (P<0.05), whereas CXCR4 mRNA expression was shown to be significantly upregulated (P<0.05). Likewise, in gastric carcinoma patients undergoing neoadjuvant chemotherapy, CXCR4 expression was found to be significantly upregulated (P<0.05), whereas in GC patients with lymph and vein infiltration, CXCL12 mRNA expression was significantly downregulated �� hese results demon� (P<0.05). These results demon-. These results demonstrate a significant inverse association between the development and progress of GC and CXCL12/CXCR4 mRNA expression. CXCR4 mRNA upregulation was promoted under the effect of neoadjuvant chemotherapy prior to surgery in GC patients, whereas higher tumor stages with lymph and vein infiltration negatively affected CXCL12 mRNA expression.

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Changes in CXCL12/CXCR4-chemokine expression during onset of colorectal malignancies

Cited by 16 publications

References 29 publications

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

CXCL12/CXCR4 display an inverse mRNA expression profile in gastric carcinoma that correlates with tumor progression

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