Expression of the Chemokine Receptors CXCR3, CXCR4, CXCR7 and Their Ligands in Rhabdomyosarcoma

Abstract

Rhabdomyosarcomas (RMS) are soft tissue malignant tumors of childhood and adolescents. The mechanisms underlying their aggressiveness are still poorly understood. Chemokines are chemotactic proteins involved in pathological processes that have been intensely studied in several types of cancers because of their influence in migration, angiogenesis, or metastases. We analyzed the expression of the chemokine receptors CXCR3, CXCR4 and CXCR7 and their ligands CXCL9, CXCL10, CXCL11 and CXCL12, in 15 RMS samples derived from nine patients. Expression was measured in tumors and primary cultures of RMS by Real-Time Polymerase Chain Reaction, immunostaining and flow cytometry. Our results show that these receptors are widely expressed in RMS. A significant difference between CXCL12/CXCR4, CXCL12/CXCR7, CXCL11/CXCR7 expression ratios was found in alveolar versus embryonal RMS and similarly between CXCL12/CXCR4 and CXCL11/CXCR3 ratios in primary versus recurrent tumors. These findings suggest a possible association between the interrelation of chemokine/chemokine-receptor and an aggressive biological behavior in RMS.

Chemokine Receptor CXCR3 Correlates with Decreased M2 Macrophage Infiltration and Favorable Prognosis in Gastric Cancer

“…Chemokine receptors, which are a superfamily of G-protein-coupled receptors, involve in numerous biological processes, including cell adhesion and migration, by binding to their ligands [14]. Furthermore, it has been proved that chemokine receptors participate in tumor growth and progression, such as angiogenesis and metastatic dissemination [15].…”

Tumor inhibition or tumor promotion? The duplicity of CXCR3 in cancer

“…Together with CXCR3, CXCR4 and CXCR7 are also involved in cancer biology. 80,83,[120][121][122][123][124] An interesting trio crosstalk has been identified because CXCL11, which is increased in tumors from many organs, [125][126][127][128][129] also binds CXCR7 which has CXCL12 that usually binds to CXCR4, as an additional ligand. 121 CXCR4 up-regulation has been associated with metastatic dissemination to lungs and lymph nodes in breast cancer 120 and to lungs in melanoma.…”

“…Together with CXCR3, CXCR4 and CXCR7 are also involved in cancer biology 80,83,120‐124 . An interesting trio crosstalk has been identified because CXCL11, which is increased in tumors from many organs, 125‐129 also binds CXCR7 which has CXCL12 that usually binds to CXCR4, as an additional ligand 121 …”