Comparative Expression of CXCR3 Chemokine Receptor and Their Ligands (CXCL9, CXCL10 and CXCL11) in Cutaneous Melanoma Progression
A Pellin-Carcelen, D Ramos, J Martin, E Jorda, A Pellin, C Monteagudo. University of Valencia, Valencia, Spain; Hospital Clinico Universitario, Valencia, Spain
Background: Human cutaneous melanoma is responsible for a high mortality due to their metastatic potential which is considerably increased when melanoma starts growing vertically. It has been widely hypothesized that chemokines and their receptors may influence tumor progression in a variety of cancer types. The expression of CXCR3, CXCL9, CXCL10 and CXCL11 in the melanoma microenvironment has been previously reported.
Design: Eighty-seven cryopreserved melanoma samples were distributed in 5 different groups based on the thickness of primary tumour and the type of metastasis [18 thin (1mm) primary tumors, 22 thick (>1mm) primary tumors, 18 in transit metastases, 16 lymph node metastases, and 13 distant metastases]. The expression of the target genes and the control gene 18S was evaluated by the RT-Realtime PCR technique. The statistical correlation between the gene expression in the five different groups of samples was analysed with the non parametric Mann-Whitney or Kruskal-Wallis tests.
Results: The expression of the four transcripts (CXCR3, CXCL9, CXCL10 and CXCL11) was significantly higher in primary tumors than in melanoma metastases as a whole and in distant metastasis in particular. The expression of CXCL10, CXCL11 and CXCR3, but not CXCL9, was higher in thin and in thick primary tumors than in in transit and lymph node metastases. According to the ligand versus receptor comparative expression, we found a higher proportion of CXCL9 in thin primary tumors and in distant metastasis than in thick primary melanomas.
Conclusions: Our results suggest that the interaction between CXCL10 and CXCL11 with CXCR3 should have a higher influence than that of CXCL9 in lymphatic tumor dissemination. In regard to the ligand versus receptor analysis, the higher expression values of CXCL9 in thin tumors and distant metastasis than in thick primary tumours may be responsible for retaining tumor cells in the former, or guiding tumor cells to specific metastatic sites in the later. *Performed with FIS PI07/1203 grant, from Fondo de Investigacion Sanitaria, Spain.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 44, Wednesday Morning