title: The importance of microenvironment: the role of CCL8 in metastasis formation of melanoma.
abstract: We have attempted to characterize the changes occurring on the host side during the progression of human melanoma. To investigate the role of tumor microenvironment, we set up such an animal model, which was able to isolate the host related factors playing central role in metastasis formation. One of these 'factors', CCL12, was consequently selected and its behavior was examined alongside its human homologue (CCL8). In our animal model, metastasis forming primary melanoma in the host exhibited increased level of CCL12 mRNA expression. In clinical samples, when examining the tumor and the host together, the cumulative (tumor and host) CCL8 expression was lower in the group in which human primary melanoma formed lung metastasis compared to non-metastatic primary tumors. We could not detect significant difference in CCL8 receptor (CCR1) expression between the two groups. Increased migration of the examined tumor cell lines was observed when CCL8 was applied as a chemoattractant. The tumor cells and their interactions can be influenced the expression of CCL8 by dermal fibroblasts, as a significant change in the metastatic microenvironment. Furthermore, we examined changes in miRNA profile resulted by CCL8 and miR146a appears to be a promising prognostic marker for following this process.
authors: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors: Tamás
authors: T
authors: Barbai
authors: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors: Zsuzsanna
authors: Z
authors: Fejős
authors: Avidin Ltd., Szeged, Hungary.
authors: Laszlo G
authors: LG
authors: Puskas
authors: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.|MTA-SE Tumor Progression Research Group, Budapest, Hungary.
authors: József
authors: J
authors: Tímár
authors: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.|MTA-SE Tumor Progression Research Group, Budapest, Hungary.
authors: Erzsébet
authors: E
authors: Rásó
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D054412:Chemokine CCL8 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D059016:Tumor Microenvironment
chemical_list: C515453:CCL8 protein, human; C515300:CCR1 protein, human; C491224:Ccl12 protein, mouse; D054412:Chemokine CCL8; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D018945:Monocyte Chemoattractant Proteins; D054389:Receptors, CCR1
keywords: CCL8; melanoma metastasis; miR146a; microenvironment