Evaluation of stromal metalloproteinases and vascular endothelial growth factors in a spontaneous metastasis model.
This study aims to investigate MMP2 and MT1-MMP protein as well as VEGF-C and VEGF-D mRNA expression in tumor cells and distant organs considered to be targets for metastasis in a tumor spontaneous metastasis model previously described. Cultured tumor cells, able to express pro-MMP2, MMP2, pro-MMP9, and MT1-MMP, develop tumor growth and metastasis, mainly in the liver and spleen, when they are injected in the mammary pad gland of Wistar rats. Immunohistochemical studies of tumor masses showed small groups of tumor cells staining for MT1-MMP but not for MMP2. In the liver, tumor metastatic foci and a stromal positive staining for both MMP2 and MT1-MMP were shown. The spleen and lymph nodes, with only scattered metastatic cells, did not show MMPs immunostaining. Using RT-PCR, a significantly higher VEGF-C and VEGF-D gene expression was shown in the liver of tumor-bearing rats respect to normal rats, whereas spleen and lymph nodes did not show significant differences in mRNA VEGF-C/D levels. Taken together, our results suggest that the stroma microenvironment of target organs for metastasis has the ability to produce MMPs and VEGFs that facilitate the anchorage of tumor cells and promote tumor cell growth and angiogenesis.
Donadio
Ana Carolina
AC
Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba CP5000, Argentina. anacarol@bioclin.fcq.unc.edu.ar
Durand
Sandra
S
Remedi
María Mónica
MM
Frede
Silvia
S
Ceschin
Danilo Guillermo
DG
Genti-Raimondi
Susana
S
Chiabrando
Gustavo Alberto
GA
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013160:Splenic Neoplasms / Q000378:metabolism / Q000556:secondary; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis* / Q000235:genetics; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2