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CXCR4 expression affects overall survival of HCC patients whereas CXCR7 expression does not.

Neve Polimeno M, Ierano C, D'Alterio C, Simona Losito N, Napolitano M, Portella L, Scognamiglio G, Tatangelo F, Maria Trotta A, Curley S, Costantini S, Liuzzi R, Izzo F, Scala S - Cell. Mol. Immunol. (2014)

Bottom Line: Interestingly, the common CXCR4-CXCR7 ligand CXCL12 was expressed at significantly lower levels in tumor tissues compared to adjacent normal liver (P=0.032).In conclusion, CXCR4 affects the prognosis of HCC patients but CXCR7 does not.Therefore, the CXCR4-CXCL12-CXCR7 axis plays a role in the interaction of HCC with the surrounding normal tissue and represents a suitable therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Oncological Immunology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Giovanni Pascale"-IRCCS-ITALIA, Naples, Italy.

ABSTRACT
Hepatocellular carcinoma (HCC) is a heterogeneous disease with a poor prognosis and limited markers for predicting patient survival. Because chemokines and chemokine receptors play numerous and integral roles in HCC disease progression, the CXCR4-CXCL12-CXCR7 axis was studied in HCC patients. CXCR4 and CXCR7 expression was analyzed by immunohistochemistry in 86 HCC patients (training cohort) and validated in 42 unrelated HCC patients (validation cohort). CXCR4 levels were low in 22.1% of patients, intermediate in 30.2%, and high in 47.7%, whereas CXCR7 levels were low in 9.3% of patients, intermediate in 44.2% and high in 46.5% of the patients in the training cohort. When correlated to patient outcome, only CXCR4 affected overall survival (P=0.03). CXCR4-CXCL12-CXCR7 mRNA levels were examined in 33/86 patients. Interestingly, the common CXCR4-CXCR7 ligand CXCL12 was expressed at significantly lower levels in tumor tissues compared to adjacent normal liver (P=0.032). The expression and function of CXCR4 and CXCR7 was also analyzed in several human HCC cell lines. CXCR4 was expressed in Huh7, Hep3B, SNU398, SNU449 and SNU475 cells, whereas CXCR7 was expressed in HepG2, Huh7, SNU449 and SNU475 cells. Huh7, SNU449 and SNU475 cells migrated toward CXCL12, and this migration was inhibited by AMD3100/anti-CXCR4 and by CCX771/anti-CXCR7. Moreover, SNU449 and Huh7 cells exhibited matrix invasion in the presence of CXCL12 and CXCL11, a ligand exclusive to CXCR7. In conclusion, CXCR4 affects the prognosis of HCC patients but CXCR7 does not. Therefore, the CXCR4-CXCL12-CXCR7 axis plays a role in the interaction of HCC with the surrounding normal tissue and represents a suitable therapeutic target.

No MeSH data available.


Related in: MedlinePlus

CXCR4 overexpression affects overall survival in HCC patients. (a) Kaplan–Meier curve examining overall survival according to CXCR4 and CXCR7 expression in HCC patients (training cohort). (b) Validation cohort. HCC, hepatocellular carcinoma.
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fig2: CXCR4 overexpression affects overall survival in HCC patients. (a) Kaplan–Meier curve examining overall survival according to CXCR4 and CXCR7 expression in HCC patients (training cohort). (b) Validation cohort. HCC, hepatocellular carcinoma.

Mentions: To evaluate the prognostic role of CXCR4 and CXCR7 in HCC, the overall survival and progression-free survival were evaluated in 86 HCC patients as a training cohort and in 42 unrelated HCC patients as a validation cohort (Supplementary Table 1). Kaplan–Meier curves based on CXCR4 expression revealed that high CXCR4 expression predicted relatively poor overall survival in both cohorts, whereas CXCR7, which was widely expressed, did not significantly correlate with prognosis (Figure 2).


CXCR4 expression affects overall survival of HCC patients whereas CXCR7 expression does not.

Neve Polimeno M, Ierano C, D'Alterio C, Simona Losito N, Napolitano M, Portella L, Scognamiglio G, Tatangelo F, Maria Trotta A, Curley S, Costantini S, Liuzzi R, Izzo F, Scala S - Cell. Mol. Immunol. (2014)

CXCR4 overexpression affects overall survival in HCC patients. (a) Kaplan–Meier curve examining overall survival according to CXCR4 and CXCR7 expression in HCC patients (training cohort). (b) Validation cohort. HCC, hepatocellular carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496532&req=5

fig2: CXCR4 overexpression affects overall survival in HCC patients. (a) Kaplan–Meier curve examining overall survival according to CXCR4 and CXCR7 expression in HCC patients (training cohort). (b) Validation cohort. HCC, hepatocellular carcinoma.
Mentions: To evaluate the prognostic role of CXCR4 and CXCR7 in HCC, the overall survival and progression-free survival were evaluated in 86 HCC patients as a training cohort and in 42 unrelated HCC patients as a validation cohort (Supplementary Table 1). Kaplan–Meier curves based on CXCR4 expression revealed that high CXCR4 expression predicted relatively poor overall survival in both cohorts, whereas CXCR7, which was widely expressed, did not significantly correlate with prognosis (Figure 2).

Bottom Line: Interestingly, the common CXCR4-CXCR7 ligand CXCL12 was expressed at significantly lower levels in tumor tissues compared to adjacent normal liver (P=0.032).In conclusion, CXCR4 affects the prognosis of HCC patients but CXCR7 does not.Therefore, the CXCR4-CXCL12-CXCR7 axis plays a role in the interaction of HCC with the surrounding normal tissue and represents a suitable therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Oncological Immunology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Giovanni Pascale"-IRCCS-ITALIA, Naples, Italy.

ABSTRACT
Hepatocellular carcinoma (HCC) is a heterogeneous disease with a poor prognosis and limited markers for predicting patient survival. Because chemokines and chemokine receptors play numerous and integral roles in HCC disease progression, the CXCR4-CXCL12-CXCR7 axis was studied in HCC patients. CXCR4 and CXCR7 expression was analyzed by immunohistochemistry in 86 HCC patients (training cohort) and validated in 42 unrelated HCC patients (validation cohort). CXCR4 levels were low in 22.1% of patients, intermediate in 30.2%, and high in 47.7%, whereas CXCR7 levels were low in 9.3% of patients, intermediate in 44.2% and high in 46.5% of the patients in the training cohort. When correlated to patient outcome, only CXCR4 affected overall survival (P=0.03). CXCR4-CXCL12-CXCR7 mRNA levels were examined in 33/86 patients. Interestingly, the common CXCR4-CXCR7 ligand CXCL12 was expressed at significantly lower levels in tumor tissues compared to adjacent normal liver (P=0.032). The expression and function of CXCR4 and CXCR7 was also analyzed in several human HCC cell lines. CXCR4 was expressed in Huh7, Hep3B, SNU398, SNU449 and SNU475 cells, whereas CXCR7 was expressed in HepG2, Huh7, SNU449 and SNU475 cells. Huh7, SNU449 and SNU475 cells migrated toward CXCL12, and this migration was inhibited by AMD3100/anti-CXCR4 and by CCX771/anti-CXCR7. Moreover, SNU449 and Huh7 cells exhibited matrix invasion in the presence of CXCL12 and CXCL11, a ligand exclusive to CXCR7. In conclusion, CXCR4 affects the prognosis of HCC patients but CXCR7 does not. Therefore, the CXCR4-CXCL12-CXCR7 axis plays a role in the interaction of HCC with the surrounding normal tissue and represents a suitable therapeutic target.

No MeSH data available.


Related in: MedlinePlus